Ex Parte MULDOON et alDownload PDFPatent Trial and Appeal BoardDec 15, 201714210630 (P.T.A.B. Dec. 15, 2017) 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. 02911.012660. 1015 EXAMINER BASQUILL, SEAN M ART UNIT PAPER NUMBER 1613 MAIL DATE DELIVERY MODE 14/210,630 03/14/2014 Brendan MULDOON 5514 7590 12/15/2017 FITZPATRICK CELLA HARPER & SCINTO 1290 Avenue of the Americas NEW YORK, NY 10104-3800 12/15/2017 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 PATENT TRIAL AND APPEAL BOARD Ex parte BRENDAN MULDOON and STEPHEN MCCULLAGH Appeal 2016-006885 Application 14/210,63 01 Technology Center 1600 Before ULRIKE W. JENKS, JOHN G. NEW, and RACHEL H. TOWNSEND, Administrative Patent Judges. TOWNSEND, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to a soft gelatin capsule dosage form, which have been rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm. STATEMENT OF THE CASE “[Sjoft gelatin capsules have been known to have a decrease in dissolution during storage, which eventually may retard or deleteriously impact drug release.” (Spec. 13.) Appellant’s “invention relates to a 1 Applicant is the Appellant, which is Warner Chilcott Company, LLC, also identified as the Real Party in Interest. (Appeal Br. 1.) Appeal 2016-006885 Application 14/210,630 pharmaceutical soft gelatin capsule dosage form that has a stable dissolution profile over the time of storage.” {Id. 12.) Claims 1, 3—9, 11 and 12 are on appeal. Claim 1 is representative and reads as follows: 1. A pharmaceutical soft gelatin capsule dosage form comprising: a shell comprising gelatin and a plasticizer; and a fill comprising at least one pharmaceutically active ingredient, polyethylene glycol, polyacrylic acid, a neutralizing agent, and water, wherein the neutralizing agent is a primary amine or a secondary amine and is present in an amount of about 0.05% to about 0.5% by weight of the total weight of the fill so as to provide a soft gelatin dosage form having stable dissolution after storage, and wherein stable dissolution after storage is achieved when the soft gelatin capsule stored for one month at 40°C and a relative humidity of 75% had less than about 30% change in dissolution after one month storage. (Appeal Br. 10.) The following grounds of rejection by the Examiner are before us on review: Claims 1 and 3—9 under 35 U.S.C. § 103(a) as unpatentable over Gao2 and Acharya.3 Claims 11 and 12 under 35 U.S.C. § 103(a) as unpatentable over Gao, Acharya, and Zeng.4 2 Gao, US 2004/0131670 Al, published July 8, 2004. 3 Acharya, US 5,102,666, issued Apr. 7, 1992. 4 Zeng et al., US 2007/0104778 Al, published May 10, 2007. 2 Appeal 2016-006885 Application 14/210,630 DISCUSSION Obviousness over Gao and Acharya The Examiner finds that Gao teaches soft gelatin capsule dosage forms that provide a stable and predictable dissolution rate of drugs that have a low water solubility after storage. (Final Action 3.) The Examiner notes that the capsules include a shell that contains gelatin, a primary or secondary amine, and plasticizers. (Id.) The fill material includes polyethylene glycol and water (as a cosolvent), and optionally includes a primary or secondary amine, such as diethanolamine. (Id. at 4.) The Examiner explains that Gao teaches that if an amine is included, the total amount in the dosage form should be within the range of about 0.1 —2 % of the composition, with most preferably 70% of the amine being present in the shell. (Id.) The Examiner contends, therefore, that “in a most preferred embodiment, Gao indicates that the fill material contains between 0.03-0.6% of the primary or secondary amines contained within the composition as a whole, overlapping the ranges of the instant claims.” (Id.) The Examiner further notes that Gao teaches the fill material may also optionally include a wetting agent such as a surfactant, hydrophilic polymer or certain clays, which would serve to aid in the dissolution and/or dispersion of a hydrophobic drug. (Id.) The Examiner recognizes that Gao does not teach inclusion of a polyacrylic acid, e.g., polycarbophil, as the hydrophilic polymer being including in the fill material, but contends that it would have been obvious to include that ingredient in light of the teachings of Acharya. (Id. at 4—5.) In particular, explains the Examiner, Acharya teaches that polycarbophil when combined with water and other cosolvents, such as polyethylene glycol, 3 Appeal 2016-006885 Application 14/210,630 provides for controlled release of pharmaceutical active agents incorporated into a matrix, including estrogens and other steroids. (Id. at 4.) According to the Examiner, Acharya teaches that compositions including polycarbophil are “capable of being formulated into any of a variety of physical forms, including capsules.” (Id. at 5.) In light of these teachings, the Examiner concludes that it would have been obvious to one of ordinary skill in the art to have selected polycarbophil as the hydrophilic polymer to be included in the Gao composition to aid in the dissolution and dispersion of the active in Gao with controlled release. We agree with the Examiner’s factual findings and conclusion that the claimed capsule dosage form would have been obvious to one of ordinary skill in the art in light of the teachings of Gao and Acharya. Appellant argues that incorporating a primary or secondary amine in a capsule fill composition in an amount of about 0.05 to about 0.5% by weight of the fill would not have been obvious to one of ordinary skill in the art because “the problem of decreased dissolution during storage of soft gelatin capsules containing a polyacrylic acid fill” was not recognized at the time of Appellant’s invention. (Appeal Br. 3.) We do not find this argument persuasive. As the Examiner explained, Gao teaches a capsule formulation where a primary or secondary amine is included in the fill at about 30% of 0.1—2% by weight of the composition. (Gao 28, 110-111; Final Action 4.) In other words, the amine is included in the fill at between about 0.03— 6%. This range overlaps the claimed range. Therefore, the issue for obviousness is not whether it would have been obvious to incorporate an amine in the capsule fill material in the claimed range, but rather, whether it would have been obvious to select a polyacrylic 4 Appeal 2016-006885 Application 14/210,630 acid, like polycarbophil, as the hydrophilic polymer to include in the Gao fill composition that includes an amine in the claimed range. We agree with the Examiner that in light of the teachings of Acharya, one of ordinary skill in the art would have found it obvious to include such a hydrophilic polymer. As the Examiner noted (Final Action 4—5; see also Ans. 8), Acharya teaches that the combination of calcium polycarbophil with water and/or other cosolvents “provides a means for achieving a rate-controlled release of the active composition.” (Acharya 2:64—3:6.) Furthermore, Acharya teaches that the dosage form for which the compositions are “especially useful” includes encapsulated capsules (id. atl: 10—14) and that the polymeric system and active composition can be “in either dry form, as a semi-solid or as a liquid suspension” (id. at 8:48—52). Thus we disagree with Appellant’s apparent position that Acharya only “suggests the way the composition would be encapsulated in a gelatin capsule would be to prepare a dry granulation” (Appeal Br. 7). “When determining the patentability of a claimed invention which combines two known elements, ‘the question is whether there is something in the prior art as a whole to suggest the desirability, and thus the obviousness, of making the combination.’” In re Beattie, 974 F.2d 1309, 1311-12 (Fed. Cir. 1992) (quoting Lindemann Maschinenfabrik GMBH v. American Hoist & Derrick Co., 730 F.2d 1452, 1462 (Fed. Cir. 1984)). Appellant argues that Acharya “does not provide adequate suggestion or motivation for substituting the polycarbophil of Acharya into the liquid filled capsule of Gao.” (Appeal Br. 6.) However, for the reasons just discussed, we find that the Examiner has provided evidence from the prior art that there is a suggestion of the desirability of using polycarbophil as the 5 Appeal 2016-006885 Application 14/210,630 hydrophilic polymer of the Gao fill formulation. Moreover, contrary to Appellant’s argument (Appeal Br. 4, Reply Br. 2), “we do not view the rejection as deficient merely because [A]ppellant[] allege[s] a different advantage resulting from” the inclusion of a primary or secondary amine in the particularly claimed percentage when polycarbophil is also included in the fill composition. In re Kronig, 539 F.2d 1300, 1304 (CCPA 1976). Appellant argues that Gao does not teach or suggest the use of polyacrylic acid. (Appeal Br. 4.) This argument is not persuasive in that the Examiner relied on Acharya for the obviousness of selecting this hydrophilic polymer for the composition taught by Gao. For similar reasons, we do not find persuasive Appellant’s argument that Acharya does not “suggest using a primary or secondary amine” as claimed {id. at 6—7). The Examiner relied upon Gao for such a teachings. “Non-obviousness cannot be established by attacking references individually where the rejection is based upon the teachings of a combination of references. . . . [The reference] must be read, not in isolation, but for what it fairly teaches in combination with the prior art as a whole.” In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986). Appellant further argues that Gao teaches away from the “addition” of a primary or secondary amine in the claimed amount. (Appeal Br. 5, Reply Br. 2—3.) We do not find this argument persuasive. Gao teaches fill compositions that include tromethamine. (Gao 1135 (Example 3).) And as discussed above Gao teaches that the fill composition can include a primary or secondary amine in the range of from about 0.03% —0.6% {id. ]ff[ 28, 110— 111), a range that fully overlaps the claims range of 0.05-0.5% claimed. It is true, as Appellant contends (Appeal Br. 5, Reply Br. 3), that a specific fill composition of Gao that includes 0.5% tromethamine resulted in pellicle 6 Appeal 2016-006885 Application 14/210,630 formation after 4 weeks. (Gao 1135 (Table 5) and 1136 (Table 6) and 1 137.) However, Gao’s example F3 also included 3.3% dimethylethanolamine (DMAE). (Id.) Fill formulation 1 (FI) that includes tromethamine at 2.6% and no dimethylethanolamine (DMAE) or other primary or secondary amine resulted in no pellicle formation after 4 weeks. (Id.) Thus, Gao indicates that lowering the amount of total primary and secondary amine can assist in preventing pellicle formation. Consequently, we do not find the single fill formulation that employs 0.5% tromethamine in a particularly described formulation that also includes DMAE in 3.3% that results in pellicle formation on storage to teach away from the claimed range of including a primary or secondary amine in an amount of about 0.05% to about 0.5%, where Gao specifically describes including a primary or secondary amine in the fill in a range of from 0.03% to 0.6%. Furthermore, Appellant has not established unexpected properties in the claimed range. In re Geisler, 116 F.3d 1465, 1469 (Fed. Cir. 1997)(“[A] prima facie case of obviousness based on overlapping ranges can be rebutted if the applicant (1) can establish ‘the existence of unexpected properties in the range claimed’ or (2) can show ‘that the art in any material respect taught away’ from the claimed invention.”). “To be particularly probative, evidence of unexpected results must establish that there is a difference between the results obtained and those of the closest prior art, and that the difference would not have been expected by one of ordinary skill in the art at the time of the invention.” Bristol-Myers Squibb Co. v. Teva Pharms. USA, Inc., 752 F.3d 967, 977 (Fed. Cir. 2014). Rather than provide any comparison, Appellant points only to the F3 fill formulation of Gao that contained 0.5% tromethamine exhibited pellicle formation after 30 days. 7 Appeal 2016-006885 Application 14/210,630 However, Appellant fails to appreciate that the addition of tromethamine to a composition that also contained dimethylethanolamine (F3) at 3.3% resulted in less pellicle formation than a composition that contained DMAE at 3.4% and no tromethamine, i.e., composition F2. (Gao Table 5 and 6.) Combined with the fact that tromethamine used in a fill composition at 2.6% without DMAE and pellicle formation was not observed {id.), Gao suggests that tromethamine in the fill in various amounts may assist in stabilizing the formulation on storage. Thus the use of tromethamine or any other primary or secondary amine in the claimed range has not been established by Appellant to be unexpected. Claims 3—9 have not been argued separately and therefore fall with claim 1. 37 C.F.R. § 41.37(c)(l)(iv). Obviousness over Gao, Acharya, and Zeng The Examiner explains that while Gao does not teach the use of diisopropanolamine in a fill composition as claimed, selecting that amine would have been obvious in light of the teachings of Zeng. (Final Action 8.) The Examiner explains that “Zeng, . . . indicate[s] that diisopropanolamine is a pharmaceutically acceptable primary or secondary amine for use in drug delivery, particularly with controlled release gelling agent carriers such as polycarbophil” and in a capsule dosage form that contains active agents such as estradiol. {Id. at 9.) Appellant contends that “the deficiencies of Gao and Acharya” regarding claim 1 “are not remedied by Zeng.” (Appeal Br. 7.) For the reasons discussed above, we do not find the Examiner’s rejection of claim 1 over Gao and Acharya to be deficient. Consequently, Appellant does not 8 Appeal 2016-006885 Application 14/210,630 persuade us that the Examiner erred in rejection claims 11 and 12 for obviousness over Gao, Acharya, and Zeng. SUMMARY We affirm the rejection of claims 1 and 3—9 under 35 U.S.C. § 103(a) as unpatentable over Gao and Acharya. We affirm the rejection of claims 11 and 12 under 35 U.S.C. § 103(a) as unpatentable over Gao, Acharya, and Zeng. 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). AFFIRMED 9 Copy with citationCopy as parenthetical citation