Ex Parte Prisinzano

Patent Trial and Appeal BoardApr 6, 2016

12513093 (P.T.A.B. Apr. 6, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 12/513,093 03/03/2010 53137 7590 04/08/2016 VIKSNINS HARRIS & PADYS PLLP 7851 Metro Parkway Suite 325 Bloomington, MN 55425 FIRST NAMED INVENTOR Thomas Prisinzano 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. 17023.079US1 9148 EXAMINER CHANDRAKUMAR, NIZAL S ART UNIT PAPER NUMBER 1625 NOTIFICATION DATE DELIVERY MODE 04/08/2016 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): docketing@vhpglobalip.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte THOMAS PRISINZANO Appeal2013-010199 Application 12/513,093 Technology Center 1600 Before MELANIE L. McCOLL UM, JEFFREY N. FRED MAN, and JACQUELINE T. HARLOW, Administrative Patent Judges. FREDMAN, Administrative Patent Judge. DECISION ON APPEAL This is an appeal 1 under 35 U.S.C. Â§ 134 involving claims to compounds that act as opioid receptor ligands. The Examiner rejected the claims on the ground of lack of enablement. We have jurisdiction under 35 U.S.C. Â§ 6(b). We affirm. 1 Appellant identifies the Real Party in Interest as Iowa Research Foundation (see Br. 2). Appeal2013-010199 Application 12/513,093 Statement of the Case Background "Currently, there is a need for new opioid receptor ligands that have fewer side effects than known ligands. Such ligands would be useful for the treatment of diseases and conditions associated with the activity of opioid receptors" (Spec. 2, 11. 22-24). The Claims Claims 4---6, 13-15, 18, 19, 21, 22, 27, 30, and 48-53 are on appeal.2 Independent claim 21 is representative and reads as follows: 21. A compound of formula (II): (Il) wherein: Ri is hydroxy, (C1--C6)alkoxy, aryloxy, heteroaryloxy, aryl(C1--C6) alkoxy, heteroaryl(C1--C6)alkoxy, formyloxy, acetoxy, R:C(=O)O-, RbS(=0)20- methoxyoxalyloxy, trimethylsilyloxy, imidazole-1-ylthiocarbonyloxy, methoxymethoxy, aminocarbonyloxy, l-imino-2,2,2- trichloroethoxy, phenylaminocarbonyloxy, allylaminocarbonyloxy, bromo, azido, amino, acetylamino, phenylcarbonylamino, methylsulfonylamino, or phenylsulfonylamino; R2 is methoxycarbonyl; R3 is H; Riis H; 2 Claims 27 and 28 were allowed, and claims 1-3, 7-12, 16, 17, 20, 23-26, and 31--47 were cancelled (see Adv. Action 11/26/2012). 2 Appeal2013-010199 Application 12/513,093 Rs is H; R6 is (C1--C6)alkyl, (C1--C6)cycloalkyl, aryl, Het, carboxy, RjRkNC(=O)-, or heteroaryl; each Rb is independently H, (C1--C6)alkyl, (Cz- C6)alkenyl, aryl, heteroaryl, aryl(C1--C6)alkyl, Het, Het(C1- C6)alkyl, or heteroaryl(C1--C6)alkyl; each R: is independently H, (Cz-C6)alkyl, (Cz- C6)alkenyl, (Cz-C6)alkoxycarbonyl, aryl, heteroaryl, aryl(C1- C6)alkyl, Het, Het(C1--C6)alkyl, or heteroaryl(C1--C6)alkyl; each Rj and Rk is independently H, (C1--C6)alkyl, (C1- C6)alkenyl, aryl, heteroaryl, aryl(C1--C6)alkyl, Het, Het(C1- C6)alkyl, or heteroaryl(C1--C6)alkyl; wherein any aryl or heteroaryl ofR1, R6, Rb-Re, and Rr Rk is optionally substituted with one or more halo, hydroxy, (C1--C6)alkyl, (C1--C6)alkoxy, (C1--C6)alkanoyloxy, (C1- C6)alkoxycarbonyl, cyano, nitro, trifluomethyl, trifluoromethoxy, RtS(=0)2-, or RuRvN; each Rt is independently H, (C1--C6)alkyl, (Cz- C6)alkenyl, aryl, heteroaryl, aryl(C1--C6)alkyl, Het, Het(C1- C6)alkyl, or heteroaryl(C1--C6)alkyl; wherein any aryl or heteroaryl of Rt is optionally substituted with one or more halo, hydroxy, (C1--C6)alkyl, (C1- C6)alkoxy, (C1--C6)alkanoyloxy, (C1--C6)alkoxycarbonyl, cyano, nitro, trifluomethyl, trifluoromethoxy, or RuRvN; wherein any Het ofR1, R6, Rb,R:, and Rr Rk is optionally substituted with one or more halo, hydroxy, (C1--C6)alkyl, (C1- C6)alkoxy, (C1--C6)alkanoyloxy, (C1--C6)alkoxycarbonyl, cyano, nitro, trifluomethyl, trifluoromethoxy, oxo (=O), thioxo (=S), RqS(=0)20-, aryl, heteroaryl, or RuRvN; each Rq is independently H, (C1--C6)alkyl, (Cz- C6)alkenyl, aryl, heteroaryl, aryl(C1--C6)alkyl, Het, Het(C1- C6)alkyl, or heteroaryl(C1--C6)alkyl; and each Ru and Rv is independently Hor (C1--C6)alkyl; or a salt thereof. 3 Appeal2013-010199 Application 12/513,093 The Issue The Examiner rejected claims 4---6, 13-15, 18, 19, 21, 22, 27, 30, and 48-53 under 35 U.S.C. Â§ 112, first paragraph, for lack of enablement (Ans. 5-15). The issue with respect to this rejection is: Does the evidence of record support the Examiner's conclusion that the claims fail to comply with the enablement requirement? Findings of fact Breadth of Claims 1. The Examiner finds that the claims require hydrogen in the R3 and Ri position of Formulas I and II as shown below: R5 (Ans. 6-7). Presence of Working Examples 2. The Examiner finds that "[t]here is no Example of any compound corresponding to the above formulae [with hydrogen in the R3 and Ri positions] disclosed in the specification" (Ans. 9 (emphasis in original). 4 Appeal2013-010199 Application 12/513,093 Amount of Direction and Guidance Presented 3. The Specification states that "[a] compound of formula I can generally be prepared ... as illustrated in the following Scheme I. Scheme (f) (Spec. 16, 11. 19--28). 4. The Examiner finds that "[t]his generic scheme [Scheme (I)] relates to generic formula with respect to R3 and R4 groups and is not limiting as instantly claimed which requires that R3 and R4 must be hydrogens" (i\.ns. 8). 5. Example 1 of the Specification is reproduced below: (Spec. 18, 11. 16-20). 6. The Examiner finds that: These Examples [ 1--4] are limiting to the possibilities of R3 and R4 as CH3 (methyl) groups. The starting material for all 5 Appeal2013-010199 Application 12/513,093 these Examples is the Natural product Salvinorin A shown in Example 1 (first structure on page 18): 1/0 ox '("'Cfit' ~ ~ co,i.fr (Natural product Salvinorin A). (Ans. 8). State of the Art and Unpredictability of the Art 7. Dorwald 3 teaches that: The ratio of successful to unsuccessful chemical experiments in a normal research laboratory is far below unity, and synthetic research chemists, in the same way as most scientists, spend most of their time working out what went wrong, and why. Despite the many pitfalls lurking in organic synthesis, most organic chemistry textbooks and research articles do give the impression that organic reactions just proceed smoothly and that the total synthesis of complex natural products, for instance, is maybe a labor-intensive but otherwise undemanding task. In fact, most syntheses of structurally complex natural products are the result of several years of hard work by a team of chemists, with almost every step requiring careful optimization. The final synthesis usually looks quite different from that originally planned, because of unexpected difficulties encountered in the initially chosen synthetic sequence. (Dorwald preface). 3 Dorwald F., Side Reactions in Organic Synthesis, preface and 1- 15 (2005). 6 Appeal2013-010199 Application 12/513,093 8. Dorwald teaches that "even structurally simple compounds often tum out not to be so easy to make as initially thought" (Dorwald 2). "As will be shown throughout this book, the outcome of organic reactions is highly dependent on all structural features of a given starting material, and unexpected products may readily be formed" (Dorwald 8). 9. Dorwald teaches Even the most experienced chemist will not be able to foresee all potential pitfalls of a synthesis, specifically so if multifunctional, structurally complex intermediates must be prepared. The close proximity or conformational fixation of functional groups in a large molecule can alter their reactivity to such an extent that even simple chemical transformations can no longer be performed. Small structural variations of polyfunctional substrates might, therefore, bring about an unforeseeable change in reactivity (Dorwald 9). 10. Cunningham4 is post-filing date art. Cunningham does not teach any analogues of Salvinorin A, with H at the R3, ~ and R5 positions. Figure 2 is reproduced in part below: f'l, R~ 1~~-q ~~:tR~ '\ .. -Â·Â·'Â·Â·ti:, H 9 ~i r .... ~~~.-(? iâ€¢C(\ .. rlÂ·T< /[o f, (, MO,Â·,,_..XH ~~ 1 : u ..--- , , . .:.: :s: Cl.)~~v~~ CO?:Me 10 Scheme 1 depicts various modifications of Salvinorin (Holden 6112). 5 Holden et al., Synthetic studies of neocledarone diterpenes from Saliva divinonorum: Exploration of the I -position, 17 Bioorg. Med. Chem. Letters 6111--6115 (2007). 8 Appeal2013-010199 Application 12/513,093 12. Vorthenns 6 is post-filing date art. Vortherms does not teach any analogues of Salvinorin A that have H at the R3 and Ri positions. Figure 3 of Vorthenns is reproduced below: 0 R/Â· .. Â·.,_.L,y __ .2,f--~~-.0 ..... -":.::Â· Â·Â·t ..... ..._ __ /_, R. -~s r:H--=CH}::o_ 1G C:H:-C(O}N~C~) ll <')'.''':iGH,+C:HN(l-1) 'ta C~\OCH:_o i~ Ph-CO~. M 4Â·8:~Â·f-'~~(';G~ 22 // ___ Q --...._ ,-<.-Â·Â· ' ;< 1"~-() ?<>;.-,., . .-',f_--_: __ ,J.-\.o I(.;;~>) f ,_, I) 0 .â€¢. -,. -~ 0 '' :-Â·-Â· H D o'Â· "Figure 3. Structures of salvinorin A and representative derivatives. Representative modifications to the salvinorin A structure are shown for the indicated positions" (Vortherms 260). 6 Vortherms et al., Salvinorin A: From Natural Product to Human Therapeutics, 6(5) Mol. Interventions 257-265 (2006) ("Vortherms"). 9 Appeal2013-010199 Application 12/513,093 13. Prisinzano 7 is post-filing date art. Prisinzano does not teach any analogues of Salvinorin A that have H at the R3 and Ri positions. Figure 3 of Prisinzano is reproduced in part below: 12 0.Ac 13 Ok 14 OH 1$ OH 16 0 17 OH Hl OH OAc 0 f:}~H OH 0 ~LH OAe 0 ~-H OH 0 !J-H OA.c 0 o:-H OH 0 [3-H OH OH fLH 19 OH H 20 OH H 21 H H 22 OH H 23 OH H 24 OH OH CH3 CH_zOH CH~~OAc CH:;:OAc CHO CH.