Agile Therapeutics, Inc.

Patent Trials and Appeals Board

Jan 25, 2022

2021002188 (P.T.A.B. Jan. 25, 2022)

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. 16/045,338 07/25/2018 Charles G. ARNOLD 34087-136(10- Anti USCnt2) 2508 26691 7590 01/25/2022 POTTER ANDERSON & CORROON LLP ATTN: JANET E. REED, PH.D. P.O. BOX 951 WILMINGTON, DE 19899-0951 EXAMINER BERRIOS, JENNIFER A ART UNIT PAPER NUMBER 1613 NOTIFICATION DATE DELIVERY MODE 01/25/2022 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): UsPatents@potteranderson.com jgriffin@potteranderson.com rward@potteranderson.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte CHARLES G. ARNOLD, AGIS KYDONIEUS, THOMAS M. ROSSI, and ALFRED F. ALTOMARI 1 Appeal 2021-002188 Application 16/045,338 Technology Center 1600 Before ERIC B. GRIMES, TAWEN CHANG, and RACHEL H. TOWNSEND, Administrative Patent Judges. GRIMES, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134(a) involving claims to a therapeutic composition, which have been rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. 1 Appellant identifies the real party in interest as Agile Therapeutics, Inc. Appeal Br. 3. “Appellant” refers to “applicant” as defined in 37 C.F.R. § 1.42. Appeal 2021-002188 Application 16/045,338 2 STATEMENT OF THE CASE “One aspect of the invention features [a] composition for transdermal delivery of a progestin that comprises: (a) a carrier, (b) a progestin, (c) a skin permeation enhancer and (d) an antioxidant.” Spec. 1. “In certain embodiments, the progestin is levonorgestrel.” Id. at 2. The “composition can also include a humectant. In certain embodiments, the humectant is PVP.” Id. at 3. The Specification states that certain components of a transdermal composition . . . contribute to degradation of levonorgestrel. Such components include the polyacrylate pressure sensitive adhesive (“PSA”), the PVP humectant (e.g., PVP/VA), and the dimethyl sulfoxide skin permeation enhancer. Incorporation of an excipient that functions as an antioxidant can protect the progestin from degradation, i.e., it can slow degradation of the progestin, and thereby increase the shelf life of the composition. Id. at 5. Claims 1-14 are on appeal. Claim 1, reproduced below, is illustrative: 1. An adhesive polymer matrix composition for transdermal delivery of levonorgestrel, wherein: (a) the composition comprises the levonorgestrel, an anti-oxidant, and a skin permeation enhancer in a polyacrylate pressure sensitive adhesive (PSA); (b) the composition comprises at least one component that contributes to oxidative degradation of the levonorgestrel, wherein the at least one component is one or more of (i) the polyacrylate PSA, (ii) the skin permeation enhancer wherein the enhancer comprises dimethyl sulfoxide (DMSO), and (iii) polyvinyl pyrrolidone (PVP) or a PVP copolymer; (c) (i) the anti-oxidant is not an estrogen; (ii) the anti- oxidant is not a sulfoxide or a fatty acid; and (iii) the anti-oxidant protects against oxidative degradation of the levonorgestrel by the one or Appeal 2021-002188 Application 16/045,338 3 more of the PSA, the DMSO and the PVP or PVP copolymer; and (d) the stability of the composition is improved over the stability of such composition lacking the anti- oxidant. OPINION Claims 1-14 stand rejected under 35 U.S.C. § 103(a) as obvious based on Chiang,2 Funke,3 and Chien.4 Final Action5 5. The Examiner finds that “Chiang teaches transdermal delivery systems for administering estrogen and/or a progestin,” where “[t]he drug reservoir includes the active agent(s), an organic acid as the permeation enhancer, and an additional vehicle.” Id. The Examiner finds that Chiang also teaches that its system “comprises an adhesive matrix . . . such as polyacrylate adhesive copolymers,” and also teaches that suitable progestins include levonorgestrel. Id. at 5-6. The Examiner finds that “Chiang further teaches that the adhesive layer can include an antioxidant to protect against light-induced oxidation, chemically induced oxidation and thermally-induced oxidative degradation during processing and/or storage.” Id. at 6. The Examiner finds that “Funke teaches drug delivery systems and discloses that oxidative degradation of estrogens and progestins is well known in the art.” Id. The Examiner concludes that it would have been obvious “to include an anti-oxidant in the transdermal delivery system of Chiang as this is specifically contemplated 2 US 2006/0121102 A1, published June 8, 2006 3 WO 2009/100871 A2, published Aug. 20, 2009. 4 US 7,045,145 B1, issued May 16, 2006. 5 Office Action mailed March 5, 2020. Appeal 2021-002188 Application 16/045,338 4 by Chiang and Funke teaches that progestins are known to suffer from oxidative degradation.” Id. The Examiner finds that “Chiang does not teach [its] formulation to further comprise DMSO and PVP/VA,” but “Chien discloses a transdermal contraceptive delivery system comprising estrogen and a progestin, such as levonorgestrel.” Id. at 7. “Chien teaches that the delivery system comprises an adhesive polymer matri[x] preferably fabricated from a polyacrylate adhesive . . . and teaches that the system also comprises a combination of skin permeation enhancers which include a mixture of DMSO and lauryl lactate.” Id. “Chien also teaches that the system can further comprise a plasticizer/humectant such as PVP/VA copolymer.” Id. The Examiner concludes that it would have been obvious to modify the teachings of Chiang with those of Chien and add DMSO and capric acid to the formulation of Chiang, which already comprises lauryl lactate, as Chien teaches that DMSO, capric acid and lauryl lactate . . . greatly enhanced the amounts of progestin and estrogen that are dissolved in the delivery system. Id. at 8. The Examiner also concludes that it would have been obvious “to add a plasticizer/humectant such as PVP/VA copolymer as Chien teaches that this acts to regulate moisture content of the formulation and . . . reduce[s] skin irritation.” Id. The Examiner finds that the functional properties recited in parts (b) and (d) of claim 1 would have been expected in the composition made obvious by the cited references. Id. Appeal 2021-002188 Application 16/045,338 5 We agree with the Examiner that the composition of claim 1 would have been obvious to a person of ordinary skill in the art based on the cited references. Chiang discloses a transdermal system . . . for the delivery of an estrogen and/or a progestin . . . composed of a backing layer and a drug reservoir layer that contains an effective amount of the active agent(s), a low molecular weight organic acid as a permeation enhancer, and an additional vehicle (which may be an additional enhancer) in an adhesive matrix selected from acrylate adhesives, silicone adhesives, and polyisobutylene adhesives. Chiang ¶ 10. Chiang states that “[t]here are numerous progestin compounds that can be delivered using the present systems, including, by way of example, . . . levonorgestrel.” Id. ¶ 30. Chiang’s “drug reservoir also includes a low molecular weight organic acid . . . , which serves as a permeation enhancer. Examples of such acids include lactic acid, citric acid,” etc. Id. ¶ 32. Chiang also states that “[t]he adhesive material providing the adhesive matrix of the drug reservoir can be an acrylate adhesive, a silicone adhesive, or a polyisobutylene (PIB) adhesive.” Id. ¶ 41. “Particularly suitable acrylate-based adhesives comprise polyacrylate adhesive copolymers. . . . These include, for example: Duro-Tak 87-900A, an acrylic non-curing pressure sensitive adhesive.” Id. ¶ 42. Finally, Chiang suggests that “[a]ntioxidants can be included in the adhesive layer to protect against light-induced oxidation, chemically induced-oxidation, and thermally-induced oxidative degradation during processing and/or storage.” Id. ¶ 58. Chiang states that suitable antioxidants include, for example, ascorbic acid, tocopherol acetate, and butylated hydroxytoluene (BHT). Id. Appeal 2021-002188 Application 16/045,338 6 Funke discloses “a drug delivery system comprising an estrogen, a progestin or a combination thereof as active ingredients.” Funke 1:8-9. Funke states that “[t]he oxidative degradation of estrogens and progestins is well known in the field and is typical[ly] an issue with reference to the shelf life of the related solid preparation.” Id. at 2:6-8 (citing references naming norethindrone acetate, ethinyl estradiol, and (levo)norgestrel). Based on the above teachings, it would have been obvious to use a polyacrylate pressure sensitive adhesive, such as Duro-Tak 87-900A, in Chiang’s transdermal system, because Chiang discloses that such adhesives are particularly suitable. Chiang ¶ 42. It would also have been obvious to include the combination of levonorgestrel and a permeation enhancer (e.g., lactic acid), because Chiang expressly suggests these choices. Id. ¶¶ 30, 32. Finally, it would have been obvious to include an antioxidant such as BHT in Chiang’s composition, because Chiang suggests that antioxidants protect against oxidation from different conditions (id. ¶ 58), and Funke states that oxidative degradation of progestins is well known and is “an issue with reference to the shelf life.” Funke 2:6-8. The combination made obvious by Chiang and Funke meets the limitations of part (b) of claim 1 because it includes a polyacrylate pressure- sensitive adhesive (PSA), and thus “at least one component . . . of (i) the polyacrylate PSA,” as recited in claim 1. The suggested combination also reasonably appears to meet the limitations of parts (c) and (d) of claim 1, because Chiang suggests including an antioxidant to protect against chemically induced-oxidation, which would reasonably encompass oxidative degradation induced by the PSA, and protecting against degradation would be reasonably expected to improve the stability of the composition. Appeal 2021-002188 Application 16/045,338 7 Thus, Chiang and Funke support a prima facie case of obviousness with respect to claim 1. Appellant argues that “Chiang teaches that an anti-oxidant ‘can be’ included, not ‘is’ or ‘should be’ included. But, Chiang provides no guidance on when an anti-oxidant would be useful, i.e., which progestins, with which combinations of ingredients would benefit from inclusion of an anti- oxidant.” Appeal Br. 16. Appellant argues that “[m]erely because Chiang allows for optional inclusion of an anti-oxidant (but never actually includes one) does not provide motivation actually to include an anti-oxidant in a transdermal composition containing a polyacrylate PSA, PVP, DMSO and levonorgestrel as presently claimed.” Id. at 17-18. This argument is unpersuasive. First, the claimed composition does not require “a polyacrylate PSA, PVP, DMSO and levonorgestrel,” as Appellant argues. Part (b) of claim 1 requires “at least one component” selected from “the polyacrylate PSA” (referring to the polyacrylate PSA recited in part (a)), DMSO (as a penetration enhancer), or PVP or a PVP copolymer. Thus, the presence of polyacrylate PSA recited in part (a) of claim 1 is sufficient to meet the “at least one component” limitation of part (b), without requiring either DMSO or PVP. Second, Chiang does not “[m]erely . . . allow[] for optional inclusion of an anti-oxidant,” as Appellant argues, but provides a specific reason to include an anti-oxidant in its composition: “to protect against light-induced oxidation, chemically induced-oxidation, and thermally-induced oxidative degradation during processing and/or storage.” Chiang ¶ 58. And Funke states that oxidative degradation of progestins is well known in the field, without qualifying that statement to apply only to certain progestins. Thus, Appeal 2021-002188 Application 16/045,338 8 the cited references provide sufficient reason to include an anti-oxidant in Chiang’s composition for transdermal systems that includes the progestin levonorgestrel. Id. ¶ 30. Appellant argues, however, that “Funke’s teachings are far afield from the specific transdermal compositions of claim 1” because its dosage forms “compris[e] a thin water-soluble film matrix, suitable for oral administration . . . , which entails very different considerations than would be applied to transdermal formulations.” Appeal Br. 16. These arguments are unpersuasive, because Chiang suggests including an anti-oxidant in its transdermal formulations in order to prevent oxidative degradation. In addition, Funke states that oxidative degradation of estrogens and progestins is well-known, without limiting that statement only to oral dosage forms. Finally, Appellant argues that “[i]t was the [inventors] who discovered that DMSO, PVP and/or the polyacrylate PSA cause degradation of levonorgestrel. . . . Thus, prior to the instant invention, there simply was no reason or motivation to add an anti-oxidant to the prior art compositions.” Appeal Br. 18. This argument is also unpersuasive. The prior art (Funke) taught that oxidative degradation of estrogens and progestins was a well-known problem and suggested (Chiang) including an anti-oxidant in a transdermal composition comprising an estrogen and/or a progestin. Thus, regardless of whether DMSO, PVP, and/or a polyacrylate PSA were known to contribute to oxidative degradation of levonorgestrel prior to Appellant’s work, the prior art nonetheless provided a reason to include an anti-oxidant in a composition containing levonorgestrel for transdermal delivery. Appeal 2021-002188 Application 16/045,338 9 We therefore affirm the rejection of claim 1 under 35 U.S.C. § 103(a) based on Chiang, Funke, and Chien. Appellant relies on the same arguments with regard to claims 2-6 and 14. Appeal Br. 19-21. With regard to claims 7-11, Appellant argues that the cited references do not teach that polyacrylate PSA, DMSO, or PVP contribute to oxidative degradation of levonorgestrel. Id. at 20. This argument is addressed above. Appellant argues that claims 12 and 13 require an additional skin permeation enhancer and “this same combination of skin permeation enhancers was disclosed by Chien, the composition of which did not contain an antioxidant.” Id. at 21. This argument is also unpersuasive because both Chiang and Chien suggest the skin permeation enhancers recited in claim 12 for transdermal progestin-containing compositions. See Chiang ¶ 40; Chien 9:49-54. Thus, the additional limitation of claims 12 and 13 would have been obvious based on the cited references. In summary, we affirm the rejection of claims 1-14 under 35 U.S.C. § 103(a) based on Chiang, Funke, and Chien. DECISION SUMMARY In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 1-14 103(a) Chiang, Funke, Chien 1-14 Appeal 2021-002188 Application 16/045,338 10 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). See 37 C.F.R. § 1.136(a)(1)(iv). AFFIRMED