Ex Parte Wen et alDownload PDFPatent Trial and Appeal BoardFeb 14, 201814172591 (P.T.A.B. Feb. 14, 2018) 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. 14/172,591 02/04/2014 Tian Wen 106150-1283 5148 30542 7590 02/16/2018 FOT FY Rr T ARDNFR T T P EXAMINER 3000 K STREET N.W. FUBARA, BLESSING M SUITE 600 WASHINGTON, DC 20007-5109 ART UNIT PAPER NUMBER 1613 NOTIFICATION DATE DELIVERY MODE 02/16/2018 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): ipdocketing @ foley. com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte TIAN WEN, LIU LIU, MINGQI LU, JIESHAN BAI, and Y. JOSEPH MO Appeal 2016-003615 Application 14/172,5911 Technology Center 1600 Before DEBORAH KATZ, ULRIKE W. JENKS, and DAVID COTTA, Administrative Patent Judges. COTTA, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims directed to method for treating tissue ischemia. The Examiner rejected the claims on appeal under 35 U.S.C. § 103(a) as obvious and on the grounds of obviousness-type nonstatutory double patenting. We reverse the obviousness rejection, affirm the double patenting rejections, and enter a new ground of rejection. 1 According to Appellants, the real party in interest is Nexmed Holdings, Inc. App. Br. 2. Appeal 2016-003615 Application 14/172,591 STATEMENT OF THE CASE The Specification discloses that “[vjasospasm is a constriction of blood vessels, resulting in ischemia of the tissue supplied by the blood vessels.” Spec. 2. “Topical agents, such as magnesium sulfate, lidocaine, papaverine and chlorpromazine have been reported to successfully relieve vasospasm.” Id. The Specification further discloses that prostaglandin Ei, a commercially available derivative of prostanoic acid, “is a vasodilator useful to maintain open blood vessels and, therefore, to treat peripheral vascular disease among other ailments.” Id. at 3. According to the Specification, “the potential benefits from transdermal delivery of prostaglandin Ei have long been recognized.” Id. However, “prior efforts at developing a topical composition for prostaglandin delivery have not been fully successful” because prior formulations did not “sufficiently permeate the skin to provide drug concentration levels comparable to those obtained from other drug delivery routes.” Id. “To overcome this problem, topical drug formulations typically include a skin penetration enhancer.” Id. The Specification discloses that a “wide variety of compounds have been evaluated as to their effectiveness in enhancing the rate of penetration of drugs through the skin.” Id. at 4. The Specification states that the inventors “found that administration of prostaglandin compositions comprising a penetration enhancer relieves constriction of a blood vessel in vasospasm and restores blood flow.” Id. The Specification discloses: “The method and compositions are useful for the relief of vasospasm in several conditions, including vasospasm occurring 2 Appeal 2016-003615 Application 14/172,591 during and following replantation surgery.” Id. “In other embodiments, the present invention provides methods of treating tissue ischemia.” Id. Claims 65—76 are on appeal. Claim 65 is illustrative and reads as follows: 65. A method of treating tissue ischemia comprising: applying directly to a surface of a tissue of a subject needing treatment of tissue ischemia a composition comprising: one or more of prostaglandin El, a pharmaceutically acceptable salt of prostaglandin El, and a Ci to C4 alkyl ester of prostaglandin El or a pharmaceutically acceptable salt thereof, wherein the dose per application is about 0.08 mg to about 0.64 mg of prostaglandin El; a penetration enhancer selected from the group consisting of an alkyl-(N-substituted amino) alkanoate, an alkyl-2-(N,N-disubstituted amino) alkanoate, an (N- substituted amino) alkanol alkanoate, an (N,N- disubstituted amino) alkanol alkanoate, a pharmaceutically acceptable salt thereof, and a mixture thereof; a shear-thinning polymer thickener selected from the group consisting of a shearthinning polysaccharide gum and a shear-thinning polyacrylic acid polymer; a lipophilic component that is selected from the group consisting of an aliphatic Ci to Cg alcohol, an aliphatic Cg to C30 ester, a liquid polyol and a mixture thereof; water and a buffer system that provides a buffered pH. App Br. 12. 3 Appeal 2016-003615 Application 14/172,591 The claims stand rejected as follows: Claims 65—76 were rejected under 35 U.S.C. § 103(a) as obvious over Buyuktimkin2 as evidenced by Clifford.3 Final Act.4 3. Claim 65—76 were rejected on the ground of nonstatutory double patenting over claims 1—27 ofU.S. Patent No. 6,046,244 (Buyuktimkin). Final Act. 11. Claim 65—76 were rejected on the ground of nonstatutory double patenting over claims 1—29 ofU.S. Patent No. 6,414,028 Bl. Id. Claim 65—76 were rejected on the ground of nonstatutory double patenting over claims 1—37 ofU.S. Patent No. 7,105,572 B2. Id. Claim 65—76 were rejected on the ground of nonstatutory double patenting over claims 1—18 ofU.S. Patent No. 6,486,207 B2. Id. Claim 65—76 were rejected on the ground of nonstatutory double patenting over claims 1—31 ofU.S. Patent No. 6,825,234 B2. Id. Claim 65—76 were rejected on the ground of nonstatutory double patenting over claims 1—32 ofU.S. Patent No. 6,323,241 Bl. Id. FINDINGS OF FACT 1. Buyuktimkin discloses “[a] topical composition ... for transdermal application of prostaglandin Ei . . . compris[ing] prostaglandin Ei, a penetration enhancer, a polysaccharide gum, a lipophilic compound, and an acidic buffer system.” Buyuktimkin Abstract. 2 Buyuktimkin et al., U.S. Patent No. 6,046,244, issued Apr. 4, 2000 (“Buyuktimkin”). 3 Clifford et al., Treatment of Vasospastic Disease with Prostaglandin Ej, 281 British Medical Journal 1031-1034 (1980) (“Clifford”). 4 Office Action mailed Jan. 14, 2015 (“Final Act.”). 4 Appeal 2016-003615 Application 14/172,591 2. Buyuktimkin discloses: “Prostaglandin Ei is a vasodilator useful to maintain open blood vessels and therefore, to treat peripheral vascular disease among other ailments.” Id. at col. 1,11. 27—29. 3. Buyuktimkin discloses: “These compositions can be used for prolonged treatment of peripheral vascular disease, male impotency and other disorders treated by prostaglandin Ei.” Id. at col. 8,11. 6—8. 4. Table 1 of Buyuktimkin is reproduced below. TABLE 1 Ibpical Pro^Agkuuuri E* OomoestLoiVi F F 0Ingre-disnt (wt %) A B c D Pint A: p.'djydiLkd ioeusi beau gum 3 3 3 3 3 3 3 water/buftV {pH 55) 8:1 81 81 83 S3 SI S': := ticrose a tea rate 0,5 0.5 0.5 0.5 0.5 0.5 Part B: p:’osiagJ:tndj>< liL 0J 0.2 0.3 0.4 0,4 0.5 0.4 ODAIF 5 5 5 5 5 5 5 ethaitoJ 5 5 5 5 5 5 10 ethyl iauiatc 5 .5 5 5 5 5 — Id. at col. 10,11. 38—50. Table 1 “contains a list of ingredients” for compositions A—G of Buyuktimkin. Id. at col. 8,1. 54. 5. Buyuktimkin discloses: “Prostaglandin Ei is well known to those skilled in the art. Reference may be had to various literature references for its pharmacological activities, side effects, and normal dosage ranges.” Id. at col. 2,11. 52—55. 6. Buyuktimkin discloses: “The quantity of prostaglandin Ei in the pharmaceutical compositions of the present invention is a therapeutically effective amount and necessarily varies according to the desired dose, the dosage form (e.g., suppository or topical), and the particular form of prostaglandin Ei used.” Id. at col. 2,11. 63—67. 7. Buyuktimkin discloses: “The resulting topical composition, when compared to exhibits the advantageous properties described above, 5 Appeal 2016-003615 Application 14/172,591 including improved prostaglandin Ei permeation and bioavailability without drug overloading, reduced skin damage and related inflammation, and increased flexibility in design of dosage forms.” Id. at col. 8,11. 1—6. 8. Buyuktimkin discloses “[application of prostaglandin Ei in a topical composition of the present invention to the skin of a patient allows a predetermined amount of prostaglandin Ei to be administered continuously to the patient.” Id. at col. 8,11. 11—14. 9. The Specification discloses “[vjasospasm is a constriction of blood vessels, resulting in ischemia of the tissue supplied by the blood vessels.” Spec. 2. ANALYSIS Obviousness Claim 65, the only independent claim on appeal, requires that the “dose per application is about 0.08 mg to about 0.64 mg of prostaglandin El.” In finding the pending claims to be obvious, the Examiner found that “Buyuktimkin teaches 0.001 gram in Table 1 and from 0.1 to 0.5% which is about 1 mg to 5 mg . . . indicating that the amount of the prostaglandin can be varied.” Ans. 6. The Examiner then concluded that this was close enough to the 0.64 mg recited in the claims to support a prima facie case of obviousness. Id. at 6—7; see also id. at 9-10. Appellants argue that Buyuktimkin discloses only the “relative amount in wt%” and that the Examiner’s assertion that Buyuktimkin discloses an “actual amount (in micro gram, mg, or g) of PGE1” is “pure speculation.” App. Br. 8. We find that Appellants have the better position. The Examiner relies on Table 1 of Buyuktimkin as disclosing a “0.08 mg to about 0.64 mg” dose 6 Appeal 2016-003615 Application 14/172,591 of prostaglandin Ei. Final Act. 6—7; Ans. 9-10. However, Table 1 discloses the weight of prostaglandin Ei only as a percentage of the total weight of the composition. FF4. Buyuktimkin does not disclose total amount of the topical composition applied. Therefore, the disclosure is insufficient to establish the amount of active ingredient applied to the tissue. Because the Examiner has not articulated any other basis on which to find that the cited prior art discloses or suggests the claimed dosage, we reverse the Examiner’s rejection of claims 65—76 as obvious over Buyuktimkin as evidenced by Clifford. New Ground of Rejection As discussed above, we disagree with the Examiner that Buyuktimkin’s Table 1 expressly discloses the claimed dosage. However, we find that the claimed dosage would have been the obvious result of routine optimization. We agree with the Examiner that the other elements of the recited claims are disclosed or suggested by Buyuktimkin. Accordingly, for the reasons discussed below, under the provisions of 37 C.F.R. § 41.50(b), we enter the following new ground of rejection: Claims 65—76 are rejected as obvious over Buyuktimkin. Buyuktimkin discloses a composition comprising prostaglandin Ei, a penetration enhancer, a polysaccharide gum, a lipophilic compound, and an acidic buffer system. FF1. While Buyuktimkin does not expressly disclose the claimed dosage as applied to the tissue, Buyuktimkin does disclose that prostaglandin Ei was “well known to those skilled in the art” and suggests consulting the literature on “normal dosage ranges.” FF5. Buyuktimkin also discloses that its composition “allows a predetermined amount of prostaglandin Ei to be administered” and provides “flexibility in design of 7 Appeal 2016-003615 Application 14/172,591 dosage forms.” FF7, FF8. Buyuktimkin further discloses varying the quantity of prostaglandin Ei present in a composition “according to the desired dose, the dosage form (e.g., suppository or topical), and the particular form of prostaglandin Ei used.” FF6. The skilled artisan would thus have recognized the quantity of prostaglandin Ei was a result effective variable. See Merck & Co. v. Bio craft Labs., Inc., 874 F.2d 804, 809 (Fed. Cir. 1989) (drug dosage limitations resulted from routine experimentation); Eli Lilly & Co. v. Teva Pharms USA, Inc., 619 F.3d 1329, 1342 (Fed. Cir. 2010) (“[Conducting clinical trials to test for an optimal dose for a drug ‘is generally a routine process[’].” (citation omitted)). Accordingly, we find that the skilled artisan would have arrived at the claimed amount of prostaglandin Ei through the process of routine optimization. In re Boesch, 617 F.2d 272, 276 (CCPA 1980) (“discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art”). In finding the pending claims obvious, the Examiner found that Buyuktimkin disclosed or suggested all of the remaining elements of claims 65—76. With respect to the limitation requiring application of the composition “to a surface of a tissue of a subject needing treatment of tissue ischemia,” the Examiner found that “[o]ne of the goals of Buyuktimkin is to keep blood vessels open which inherently meets the goal of the claims so that although, Buyuktimkin does not use the term of ‘tissue ischemia’ . . . [applying the composition] would inherently . . . produce the effect of improving tissue ischemia in skin tissue.” Final Act. 5. Alternatively, the Examiner found that “prostaglandin Ei is a vasodilator and potent inhibitor of platelet aggregation and is used to treat vasospastic disease as evidenced 8 Appeal 2016-003615 Application 14/172,591 in the background of Buyuktimkin and also by Clifford.” Id. at 5—6. The Examiner thus concluded that the skilled artisan would reasonably expect that applying Buyuktimkin’s composition would “keep blood vessels open as a vasodilator according to the background disclosure of Buyuktimkin and . . . provide prolonged treatment of peripheral vascular disease and other diseases treated with prostaglandin El.” Id. at 6. Except as discussed above, we adopt the Examiner’s findings of fact and reasoning regarding the scope and content of the Buyuktimkin as applied to claims 65—76. We find that Buyuktimkin discloses the remaining limitations of claims 65—76 (i.e., the limitations other than the amount of prostaglandin Ei present) for the reasons provided by the Examiner. Accordingly, under the provisions of 37 C.F.R. § 41.50(b), we reject claims 65—76 as obvious over Buyuktimkin. We address Appellants’ arguments below. Appellants argue that the Examiner “relies on the fact that, ‘ [i]t is known in the art that prostaglandin El is a vasodilator and potent inhibitor of platelet aggregation and is used to treat vasospastic disease” and that this statement is “unsubstantiated by evidence.” App. Br. 9 (emphasis omitted). We disagree. Buyuktimkin expressly discloses that “[pjrostaglandin Ei is a vasodilator useful to maintain open blood vessels and therefore, to treat peripheral vascular disease among other ailments” and that its compositions can be used for “treatment of peripheral vascular disease, male impotency and other disorders treated by prostaglandin Ei.” FF2, FF3. Appellants argue that “the state of the art provides no reasonable expectation of success that PGE1 would be effective in treating vasospastic disease, and teaches away or at the minimum provides no reasonable 9 Appeal 2016-003615 Application 14/172,591 motivation to use PGE1 at the claimed dosage form to treat a vasospastic disease.” App. Br. 10. Appellants cite Mohrland5 as “fail[ing] to substantiate earlier reports, including by Clifford, that a 72-hr intravenous infusion of PGE1 in patients with Raynaud’s syndrome produced clinical benefit.” Id. at 9 (emphasis omitted). We are not persuaded. Buyuktimkin discloses that prostaglandin Ei is a vasodilator (FF2) and that the disclosed composition — which, like the composition recited in the claims, includes a penetration enhancer, a polysaccharide gum, a lipophilic compound, and an acidic buffer system (FF1) — is useful to treat peripheral vascular disease. FF2, FF3. Accordingly, we agree with the Examiner that tak[ing] the teaching of Buyuktimkin, one having ordinary skill in the art at the time the invention was made would reasonably expect that topically applying a semi-solid composition containing prostaglandin Ei, polysaccharide gum, lipophilic compound, penetration enhancer and buffer system that is capable of buffering the composition at a pH of about 3 to about 7.4 (abstract; column 2, lines 9-28) to a patient’s skin would keep blood vessels open as a vasodilator according to the background disclosure of Buyuktimkin and to provide prolonged treatment of peripheral vascular disease and other diseases treated with prostaglandin El (see column 1, lines 27- 29; column 8, lines 6-8). Final Act. 6. Ischemia may result from vasospasm, a constriction of the blood vessels. FF9. While Buyuktimkin does not use the word “ischemia,” prostaglandin Ei is a vasodilator known to maintain open blood vessels. 5 Mohrland et al., A Multiclinic Placebo-Controlled, Double-Blind Study of Prostaglandin Ej in Raynaud’s Syndrom, 44 Annals of Rheumatic Diseases 754—760 (1985) (“Mohrland”). Morhland was cited by the Appellants as evidence discrediting Clifford. App. Br. 9. 10 Appeal 2016-003615 Application 14/172,591 FF2. The skilled artisan would thus have reasonably expected to be able to treat ischemia by applying Buyuktimkin’s topical composition to a patient’s skin. The Examiner cited Clifford as evidence that administering Buyuktimkin’s topical composition “would produce the effect [of] improving tissue ischemia in a skin.” Final Act. 6. Appellants argue that Mohrland “fails to substantiate” Clifford. App. Br. 9. We are not persuaded because Clifford is not necessary to our rejection. Moreover, balancing the weight of Mohrland’s inability to substantiate Clifford’s report that intravenous administration of prostaglandin Ei produced significant clinical benefit in patients with Raynaud’s syndrome against Buyuktimkin’s subsequent disclosure of a topical composition (FF1) with advantageous properties (FF7, FF8) that is useful to maintain open blood vessels (FF2) and treat peripheral vascular disease (FF2, FF3), we find that a preponderance of the evidence supports that the skilled artisan would reasonably have expected to be able to treat ischemia by applying Buyuktimkin’s topical composition to a patient’s skin. Double Patenting Appellants argue all of the double patenting rejections together. App. Br. 10—11. As the same issue is dispositive with respect to all of the Examiner’s double patenting rejections, we address them all together. The full extent of Appellants’ double patenting argument is to summarily paraphrase the claims applied,6 and then assert “[a]s is apparent, 6 For example, Appellants summarize the applied claims of three reference patents as follows: “US Patent Nos. 6,486,207; 6,825,234 and 6,323,241 claim methods for ameliorating and/or treating female sexual arousal disorder and/or erectile dysfunction.” App. Br. 11. 11 Appeal 2016-003615 Application 14/172,591 none of the cited claims suggest present claim 65.” App. Br. 11. No further exposition is provided. Appellants’ arguments are insufficient to properly raise an issue on appeal. In reLovin, 652 F.3d 1349, 1357 (Fed. Cir. 2011) (“[T]he Board reasonably interpreted Rule 41.37 to require more substantive arguments in an appeal brief than a mere recitation of the claim elements and a naked assertion that the corresponding elements were not found in the prior art. Because Lovin did not provide such arguments, the Board did not err in refusing to separately address claims 2-15, 17-24, and 31-34.”). Accordingly, we affirm the Examiner’s rejection of claims 65—76 on the ground of nonstatutory double patenting as being unpatentable over claims 1—27, 1—29, 1—37, 1—18, 1—31, and 1—32 ofU.S. Patent Nos. 6,046,244, 6,414,028 Bl, 7,105,572 B2, 6,486,207 B2, 6,825,234 B2, and 6,323,241 Bl. SUMMARY For these reasons and those set forth in the Examiner’s Answer, and the Final Office Action, we affirm each of the Examiner’s rejection of claims 65—76 on the grounds of nonstatutory obviousness-type double patenting over claims 1—27, 1—29, 1—37, 1—18, 1—31, and 1—32 ofU.S. Patent Nos. 6,046,244, 6,414,028 Bl, 7,105,572 B2, 6,486,207 B2, 6,825,234 B2, and 6,323,241 Bl. For the reasons set forth herein, we reverse the Examiner’s rejection of claims 65—76 under 35 U.S.C. § 103(a) as obvious over Buyuktimkin as evidenced by Clifford. For the reasons set forth herein, we enter a new ground of rejection for claims 65—76 under 35 U.S.C. § 103(a) over Buyuktimkin. 12 Appeal 2016-003615 Application 14/172,591 TIME PERIOD FOR RESPONSE This decision contains a new ground of rejection pursuant to 37 C.F.R. § 41.50(b). Section 41.50(b) provides “[a] new ground of rejection pursuant to this paragraph shall not be considered final for judicial review.” Section 41.50(b) also provides: When the Board enters such a non-final decision, the appellant, within two months from the date of the decision, must exercise one of the following two options with respect to the new ground of rejection to avoid termination of the appeal as to the rejected claims: (1) Reopen prosecution. Submit an appropriate amendment of the claims so rejected or new Evidence relating to the claims so rejected, or both, and have the matter reconsidered by the examiner, in which event the prosecution will be remanded to the examiner. The new ground of rejection is binding upon the examiner unless an amendment or new Evidence not previously of Record is made which, in the opinion of the examiner, overcomes the new ground of rejection designated in the decision. Should the examiner reject the claims, appellant may again appeal to the Board pursuant to this subpart. (2) Request rehearing. Request that the proceeding be reheard under §41.52 by the Board upon the same Record. The request for rehearing must address any new ground of rejection and state with particularity the points believed to have been misapprehended or overlooked in entering the new ground of rejection and also state all other grounds upon which rehearing is sought. Further guidance on responding to a new ground of rejection can be found in the MPEP § 1214.01. 13 Appeal 2016-003615 Application 14/172,591 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). See 37 C.F.R. §§ 41.50(f), 41.52(b). AFFIRMED; 37 C.F.R, $ 41.50(b) 14 Copy with citationCopy as parenthetical citation