Ex Parte ZakrzewskiDownload PDFPatent Trials and Appeals BoardApr 11, 201914477034 - (D) (P.T.A.B. Apr. 11, 2019) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 14/477,034 09/04/2014 113568 7590 04/15/2019 Perkins Coie LLP - Amarin Corporation PLC 1201 Third Avenue Suite 4900 Seattle, WA 98101 FIRST NAMED INVENTOR Joseph S. Zakrzewski 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 ATTORNEY DOCKET NO. CONFIRMATION NO. 88896-8063.USOl 8748 EXAMINER GEMBEH, SHIRLEY V ART UNIT PAPER NUMBER 1615 NOTIFICATION DATE DELIVERY MODE 04/15/2019 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): patentprocurement@perkinscoie.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte JOSEPHS. ZAKRZEWSKI 1 Appeal2018-003236 Application 14/477,034 Technology Center 1600 Before DONALD E. ADAMS, JOHN G. NEW, and DAVID COTTA, Administrative Patent Judges. NEW, Administrative Patent Judge. DECISION ON APPEAL 1 Appellant identifies Amarin Pharmaceuticals Ireland Limited as the real party-in-interest. App. Br. 1. Appeal2018-003236 Application 14/477,034 SUMMARY Appellant files this appeal under 35 U.S.C. § I34(a) from the Examiner's Final Rejection of claims 1-20. Specifically, claims 1-5, 9-12, and 19 stand rejected as unpatentable under 35 U.S.C. § I03(a) as being obvious over the combination of E. Higashihara et al., Effects of Eicosapentaenoic Acid on Biochemical Failure after Radical Prostatectomy for Prostate Cancer, 24 IN VIVO 561---66 (2010) ("Higashihara"), Fortin (US 2010/0160261 Al, June 24, 2010) ("Fortin"), Breivik et al. (US 2011/0130458 Al, June 2, 2011) ("Breivik"), M. Peet et al., Dose-Ranging Study of the Effects of Ethyl-Eicosapentaenoate in Patients With Ongoing Depression Despite Apparently Adequate Treatment With Standard Drugs, 59(10) ARCH. GEN. PSYCHIATRY 913-19 (2002) ("Peet"), and Horrobin (US 6,479,544 Bl, November 12, 2002) ("Horrobin"). Claims 1, 6-8, and 13-20 stand rejected as unpatentable under 35 U.S.C. § I03(a) as being obvious over the combination of Higashihara, Fortin, Breivik, Peet, Horrobin, E. Opalinska et al., Increasing Level of Prostate-Specific Antigen and Prostate Cancer Risk Factors among 193 Men Examined in Screening Procedure (Abstract), 58(2) ANN. UNIV. CURIE SKLODOWSKA MED. 57---63 (2003) ("Opalinska"), and D.J. Gallagher et al., Germline BRCA Mutations Denote a Clinicopathologic Subset of Prostate Cancer, 16(7) CLIN. CANCER RES. 2115-121 (2010) ("Gallagher"). We have jurisdiction under 35 U.S.C. § 6(b ). We AFFIRM. 2 Appeal2018-003236 Application 14/477,034 NATURE OF THE CLAIMED INVENTION Appellant's invention is directed to methods of treating and/or preventing prostate cancer, comprising administering to a subject in need thereof a pharmaceutical composition comprising eicosapentaenoic acid or a derivative thereof. Abstract. REPRESENTATIVE CLAIM Claim 1 is representative of the claims on appeal and recites: 1. A method of treating prostate cancer in a subject, the method comprising administering to the subject about 4 g of ethyl eicosapentaenoate per day. App. Br. 26. ISSUES AND ANALYSES We adopt the Examiner's findings, reasoning, and conclusion that the claims are prima facie obvious over the combined cited prior art. We address the arguments raised by Appellant below. A. Claims 1-5, 9-12, and 19 Issue 1 Appellant argues that the Examiner has failed to establish a prima facie case of obviousness at least because the scope and content of the prior art have not been properly discerned, actual differences between the claims and the prior art are not identified, and the requirements set forth in MPEP § 2143(I)(G) have not been articulated. App. Br. 11-12. 3 Appeal2018-003236 Application 14/477,034 Analysis The Examiner finds that Higashihara teaches treating prostate cancer with eicosapentaenoic acid. Final Act. 4 (citing Higashihara 562). However, the Examiner finds, that Higashihara does not teach that the composition dosage comprises about 4 g of eicosapentanoate per day, but rather teaches administering 2.4 g/day. Id. ( citing Higashihara Abstr.). The Examiner finds that Fortin teaches that polyunsaturated fatty acid monoglycerides are useful as cancer treating agents, and that one such polyunsaturated monoglyceride is ethyl eicosapentaenoate, which can also be used in combination with other anticancer agents. Final Act. 4 ( citing Abstr., ,r,r 97, 26). The Examiner finds that Breivik teaches treating various diseases such as coronary heart disease by administering a composition comprising high concentrations of omega-3 fatty acids from krill (Breivik ,r 44), in which the omega-3 fatty acid comprises at least 75 weight% of eicosapentaenoic acid ("EPA") and/or docosahexaenoic acid ("DHA") or, more preferably, 80 weight% EPA and DHA (Breivik ,r 52) and about 90% by weight of all fatty acids. Final Act. 5---6 (citing Breivik ,r,r 36, 44, 52). The Examiner finds Breivik additionally teaches compositions comprising both EPA and DHA. Id. at 6 (citing Breivik ,r 53). The Examiner finds that Peet teaches dose-ranging effects of ethyl- eicosapentanoate in which 1 to 4 g/day of ethyl-eicosapentanoate is administered in the treatment of depression and cardiovascular-related disease. Final Act. 6 ( citing Peet 17). The Examiner finds that Horrobin teaches using pharmaceutical formulations containing EPA, or a derivative of EPA, and arachidonic acid ("AA") for the treatment of, inter alia, prostate 4 Appeal2018-003236 Application 14/477,034 cancer in which the dosage amount is 4.0 g per day. Id. ( citing Horrobin col. 3, 11. 1-25, col. 4, 11. 8-13; see also col. 2, 11. 16-20). The Examiner concludes that a person of ordinary skill in the art would have been motivated to treat prostate cancer with EPA, as taught by Higashihara, and to incorporate into these teachings the method of treating prostate cancer taught by Fortin, Peet, and Horrobin. Final Act. 6. The Examiner further concludes that person of skill in the art would have had a reasonable expectation of success in combining the references, because the dosage ranges of the compositions taught by Breivik, Peet, and Horrobin overlap the claimed dosage of 4 g/day of ethyl-eicosapentanoate in the treatment of prostate cancer. Id. Appellant argues that the Examiner finds that Higashihara: "teaches ... treating prostate cancer with eicosapentaenoic acid (i.e. and [sic] ethyl ester ... a.k.a. Epadel)." App. Br. 12 (quoting Final Act. 4). Appellant contends that the Examiner mischaracterizes the teachings of Higashihara, asserting that Higashihara teaches administering Epadel to patients having prostate cancer, but also makes clear that the Epadel treatment had no significant effect on the outcomes of the treated prostate cancer patients compared to the control group. Id. (citing Higashihara 562, 563, Table II). Therefore, Appellant argues, Higashihara does not teach: "treating prostate cancer in a subject, the method comprising administering to the subject a pharmaceutical composition comprising about 4g of E-EP A per day," as recited by claim 1. Id. at 12-13. With respect to Fortin, Appellant disputes the Examiner's finding that paragraphs [0097]-[0098] of Fortin teach eicosapentaenoic acid and that neither of the compounds depicted in paragraph [0097] depict ethyl- 5 Appeal2018-003236 Application 14/477,034 eicosapentaenoic acid. App. Br. 12-13. The formulae of paragraph [0097] are reproduced below. ~) r, /,c=-... ......... "', ... -··············,, .. -··""··············-,~--·/··············-< ... ,,.:,·/-... ... ~ \ \-:::.::.::.::.:;.:;. .• ,. ..... , .......... ......_....,,.:::.::.::.::.::.::. ....... /' ............ ,......_:::.::.::.::.::.::.:..-·.,,.,.,, ............... _ .... " ,:;·· //···············'·'-....._ ... .-=-.. .... ~,.r·' ·············· .............. /.----4!~·-,: 1·_,,,·, ........ . \ ~ ................ -, ... -.:::::::::::::...-""/ ............ ....._ ............................... ...._..._~, Appellant asserts that the upper depicted compound is ethyl docosapentaenoate (C22:5 n-3) (Compound 2), and the lower structure on the bottom is ethyl docosahexaenoate (C22:6 n-3) (Compound 7). Id. at 13. Appellant contends that E-EP A, in contrast, has a 20-carbon backbone ( excluding the ethyl radical covalently bound to the ester), whereas the structures of paragraph [0097] each have a 22-carbon backbone. Id. Appellant asserts that E-EPA and the depicted compounds of Fortin also differ in the intermediate structural regions, particularly in the location and number of the double bonds, and not in just pendant substitutions. App. Br. 13. Appellant compares the structures of Fortin's Compound 2 and Compound 7 with E-EPA (Fortin's Compound 8), as depicted below: (- ~..-= ............... ~~_....n,....._./ '=~-~- ') These differences are significant, Appellant argues, because the carbon-carbon double bonds in Fortin's Compounds 2 and 7 and in E-EPA represent important locations for biological processes, including chemical transformations and site-specific interactions with other biomolecules. Id. Furthermore, Appellant points out, the repetitive groups in E-EP A and Compounds 2 and 7 are located in the intermediate regions of the molecules 6 Appeal2018-003236 Application 14/477,034 and not at the N-tenninal pendant groups, and are thus distinguishable from homologs at issue in In re Wilder, 563 F.2d 457 (C.C.P.A. 1977). Id. Therefore, Appellant argues, E-EPA and Compounds 2 and 7 are not homologs. Id. at 14--15. Appellant asserts that a person of ordinary skill in the art would have recognized that, although Compounds 2 and 7 share general similarities with E-EPA, the differences in chain length, number of carbon-carbon double bonds, and positions of carbon-carbon double bonds relative to the ester functional group are key technical differences that would result in significant differences in biological activity observed among different fatty acids. Id. Appellant argues further that Fortin' s only mention of E-EP A is in its presence as just one of many components of a fatty acid ethyl ester mixture. App. Br. 15. Appellant asserts that Fortin does not teach the use of the mixture of fatty acid ethy 1 esters (including E-EP A) to treat any disease or disorder. Id. With respect to Horrobin, Appellant acknowledges that the reference teaches a combination of EPA and arachidonic acid ("AA") or, in some embodiments, gamma-linolenic acid ("GLA") or dihomogamma-linolenic acid ("DGLA"). App. Br. 20 ( citing Horrobin col. 1, 11. 19-20, col. 2, 11. 20- 21 ). Appellant notes that Horrobin teaches that its compositions may include EPA and arachidonic acid in a ratio "preferably between 1: 1 and 20:1." Id. (citing Horrobin col. 2, 11. 21-22). However, Appellant asserts that Horrobin teaches EPA in combination with arachidonic acid, but not as EPA alone. Id. Therefore, Appellant contends, the Examiner failed to find to teaching or suggestion of Horrobin portion disclosing administering to the subject about 4g ofE-EPA per day. Id. 7 Appeal2018-003236 Application 14/477,034 Appellant argues further that, although Horrobin teaches administering its compositions to treat a wide range of diseases and disorders, Horrobin does not teach or suggest the benefit of using the claimed composition in treating prostate cancer over other listed diseases or disorders. App. Br. 20. We do not find Appellant's arguments persuasive. As an initial matter, we remind Appellant that: "[O]ne cannot show non-obviousness by attacking references individually where ... the rejections are based on combinations of references." In re Keller, 642 F.2d 413, 426 (C.C.P.A. 1981 ). Rather, the test for obviousness is what the combined teachings of the references would have suggested to those of ordinary skill in the art. Id. at 425. Higashihara teaches the use of E-EPA (Epadel-S) administered at a daily dose of 2.4 g to post-radical prostatectomy patients, commencing 30 days post-surgery. Higashihara Abstr., 562. Higashihara summarizes the prior art as teaching: "EPA and DHA [ docosahexaenoic acid] are promising dietary agents to reduce PSA [prostate-specific antigen] recurrence after radical prostatectomy in patients with PC [prostate cancer]." Id. at 562. Although Higashihara teaches that: "The PSA [prostate-specific antigen] recurrence rates during a mean follow-up of 53.8 months were not different between the two groups [i.e., treatment and control] (p=0.16)," Higashihara also teaches that: "A longer and/or larger intervention or docosahexaenoic acid supplementation might be necessary to identify significant preventive effects of mega-3 polyunsaturated fatty acids on PSA recurrence." Id. at Abstr. ( emphasis added). Higashihara thus directly suggests that a dosage higher than 2.4 g/day could be effective. 8 Appeal2018-003236 Application 14/477,034 Fortin is cited by the Examiner as teaching, generally, that polyunsaturated fatty acid monoglycerides are useful as cancer treating agents, and that one such polyunsaturated monoglyceride is E-EPA, which can also be used in combination with other anticancer agents. See Final Act. 4 (citing Fortin, Abstr., ,r,r 97, 26). Specifically, Fortin teaches that it was known in the prior art that: A diet containing LA (n-6 PUP A[2J) stimulated the growth and metastasis of human breast cancer cells transplanted into athymic nude mice, whereas EPA or DHA exerted suppressive effects compared with palmitic acid (PA). Thus, in agreement with the epidemiological observations, LA (n-6 PUPA) accelerates, whereas EPA and DHA (n-3 PUP A) suppress mammary cancer compared with PA diet in experimental systems (Rose D P, and al., JNCI 87, 1995) (Senzaki H, and al., Anticancer Res 18, 1998). Fortin ,r 6. Horrobin is directed to: "Eicosapentaenoic acid or any appropriate derivative (EPA) ... in combination with arachidonic acid (AA) or an AA precursor, selected from DGLA and GLA, to give a pharmaceutical formulation." Horrobin Abstr. Specifically, Horrobin teaches: The present invention provides pharmaceutical formulations containing eicosapentaenoic acid or any appropriate derivative (hereinafter collectively referred to as EPA) and arachidonic acid (AA), as set out in the claims attached. The EPA is preferably provided in a dose of between 100 mg and 10,000 mg/day. The formulation may be a single preparation comprising 100-10,000 mg EPA. An alternative upper limit is 5,000 mg EPA. Preferably, the formulations of the invention comprise 1--4 g EPA and O .1- 2 Polyunsaturated fatty acid. 9 Appeal2018-003236 Application 14/477,034 2.0 g arachidonic acid (AA). Still preferred amounts are 1.5-3 g EPA and 0.2-1 g AA. Horrobin col. 2, 11. 16-29. Horrobin further teaches that: "The EPA is preferably composed of a triglyceride or ethyl ester which is 50% pure or purer, more preferably more than 90% pure." Id. at 11. 55-57. Horrobin also teaches that: "The formulations of the present invention may be used for the treatment of a wide range of diseases and disorders including: ... disease of the male or female reproductive organs such as the breast or the prostate gland." Id. at col. 3, 11. 1-22. Appellant contends that the teachings of Horrobin are inapposite because Horrobin teaches administration of EPA in combination with AA, and not by itself. However, Appellant's independent claim 1 recites: "A method of treating prostate cancer in a subject, the method comprising administering to the subject about 4 g of ethyl eicosapentaenoate per day." Use of the transition "comprising" in the language of a claim creates a presumption that the claim does not exclude additional, unrecited elements. See Crystal Semiconductor Corp. v. Tri Tech Microelectronics Int 'l, Inc., 246 F.3d 1336, 1348 (Fed. Cir. 2001). Consequently, the scope of claim 1 does not exclude the co-administration of AA with E-EP A, as expressly taught by Horrobin. Consequently, we are not persuaded by Appellant's argument that the Examiner failed to accurately ascertain the differences between the claimed invention and the applied references. On the contrary, we agree with the Examiner that the combined cited prior art teaches or suggests the limitations of claim 1. 10 Appeal2018-003236 Application 14/477,034 Issue 2 Appellant argues that the Examiner erred because a person of ordinary skill in the art, understanding the teachings of the cited prior art, would have had no motivation to combine the references, and no reasonable expectation of success in so doing. App. Br. 20. Analysis Appellant repeats the argument, presented supra, that Higashihara teaches that administering 2.4g of Epadel per day to patients who had already undergone radical prostatectomy and had plasma PSA levels of 0.2 ng/mL or less 3 months after surgery had no significant effects compared to control. App. Br. 21 (citing Higashihara Abstr., 562, 563). Appellant also argues that the Examiner acknowledges that Fortin does not disclose administering E-EPA, in any amount, to a subject, or using E-EPA to treat any type of cancer. Id. Appellant then points to M. Y. Wei et al., Effects of Eicosapentaenoic Acid Versus Docosahexaenoic Acid on Serum Lipids: A Systematic Review and Meta-Analysis, 13 CURR. ATHEROSCLER. REP. 474--83 (2011) ("Wei"). App. Br. 22. According to Appellant, both Wei and Higashihara teach that DP A ethyl ester or DHA ethyl ester (i.e., Fortin's Compounds 2 and 7, respectfully) and are not relevant to the claims on appeal, because Higashihara expressly teaches that DHA ethyl ester likely has different biological activity in prostate cancer patients than the inactivity observed for EPA ethyl ester. Id. ( citing Higashihara 564). Appellant next argues that Breivik is relied upon by the Examiner as teaching: "treating various diseases such as coronary heart disease ... " but 11 Appeal2018-003236 Application 14/477,034 does not teach treating prostate cancer with E-EPA. App. Br. 22. Appellant also argues that Peet traches that E-EP A acts as an antidepressive agent in patients. Id. (citing Peet Abstr.). Appellant also contends that, because Peet teaches administering a dose of 1 g/day ofE-EPA. Id. (citing Peet 915-16). Therefore, argues Appellant, a person of ordinary skill in the art, understanding the combined teachings of Higashihara, Horrobin, Breivik, Peet, and Fortin would not expect to be successful in treating prostate cancer using 4g of E-EP A, because none of the applied references either alone or in combination suggest or teach administration of 4g E-EPA in the treatment of prostate cancer, as recited in claim 1. We do not agree, for the reasons we have set forth supra. Although Higashihara does not report effective results following daily post-radical prostatectomy administration of 2.4g of E-EP A, Higashihara expressly encourages the administration of higher dosages. See Higashihara Abstr. Fortin is cited generally for the purpose of establishing that the prior art recognized that polyunsaturated fatty acids, such as E-EPA, may be effective in the treatment of prostate cancer. Furthermore, Horrobin (which Appellant does not discuss in this section) teaches administration of E-EP A in the dosage recited in the claims for the treatment of, inter alia, prostate cancer. See Horrobin col. 2, 11. 16-29, 55-57, col. 3, 11. 1-22. As we have also explained, the fact that Horrobin also teaches co-administration of AA does not place the teachings of Horrobin beyond the scope of the claims on appeal. We agree with the Examiner that a person of ordinary skill in the art would be motivated to combine the teachings of the cited prior art to increase the dosage taught by Higashihara to the range taught by Horrobin, 12 Appeal2018-003236 Application 14/477,034 and as generally suggested by Fortin, and that the skilled artisan would have, based upon the combined teachings of the references, a reasonable expectation of success. See In re Langi, 759 F.2d 887, 897 (Fed. Cir. 1985) ("Only a reasonable expectation of success, not absolute predictability, is necessary for a conclusion of obviousness"). We consequently affirm the Examiner's rejection of independent claim 1. Furthermore, Appellant relies upon the same arguments with respect to the Examiner's rejection of dependent claims 2-5, 9-12, and 19. App. Br. 23. For the reasons we have explained supra, we similarly affirm the rejection of those claims. B. Claims 1, 6-8, and 13-20 Appellant argues that the teachings of Opalinska and Gallagher Fail to cure the alleged deficiencies of Higashihara, Fortin, Breivik, Horrobin, and Peet. App. Br. 24--25. We have explained in Section A of this Decision why we do not find Appellant's arguments with respect to the combined cited prior art persuasive. We incorporate those arguments herein, and we affirm the Examiner's rejection of the claims. 13 Appeal2018-003236 Application 14/477,034 DECISION The Examiner's rejection of claims 1-20 under 35 U.S.C. § 103(a) is affirmed. No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a)(l )(iv). AFFIRMED 14 Copy with citationCopy as parenthetical citation