Ex Parte Goldstein et al

Patent Trial and Appeal BoardAug 14, 2014

11899758 (P.T.A.B. Aug. 14, 2014)

UNITED STATES PATENT AND TRADEMARK OFFICE ________________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ________________ Ex parte DAVID MICHAEL GOLDSTEIN, LEYI GONG, CHRISTOPHE MICHOUD, WYLIE SOLANG PALMER, and ACHYUTHARAO SIDDURI1 ________________ Appeal 2012-004990 Application 11/899,758 Technology Center 1600 ________________ Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and ROBERT A. POLLOCK, Administrative Patent Judges. POLLOCK, Administrative Patent Judge. DECISION ON APPEAL Appellants appeal under 35 U.S.C. § 134(a) from the Examiner’s rejection of claims 1-24 and 30. We have jurisdiction under 35 U.S.C. § 6(b). We reverse. 1 Appellants identify Hoffman-La Roche Inc. as the Real Party in Interest. (App. Br. 1). Appeal 2012-004990 Application 11/899,758 2 STATEMENT OF CASE Appellants’ invention relates to benzotriazole derivatives useful in modulating c-Jun N-terminal kinases (JNK) and cyclin-dependent kinases (CDK). Exemplary independent claim 1 recites: 1. A compound of the formula: or a pharmaceutically acceptable salt thereof, wherein R is lower alkyl, hydroxy lower alkyl, or a radical selected from: each Ra is independently H, lower alkyl, OH, or hydroxy-lower alkyl; each Rb is independently H, lower alkyl, halo, nitro, or halo-lower alkyl; p is 1, 2, 3, or 4; X is O, CR4R5, C(=O), or S(O)x; Rl is hydrogen, halo, alkyl, or NH2; each of R3 is independently halo, -NO2, lower alkyl, -CN, -OR7, -NR8R9, - C(O)-R7,-O-C(O)-R7, -CF3, -CHF-, -S02-R10, or two of R3 form alkylene dioxy; R4 is hydrogen, lower alkyl, cyano, -(CH2)nOR7, -(CH2)nNR8R9, -(CH2)n- C(O)-NR8R9,-(CH2)n-OC(O)-NR8R9, -(CH2)n-C(O)-OR7; -NR7-SO— R10=, -(CH2)n-NR8-C(O)-Rll, or -(CH2)n-NR8-C(O)-OR6; R5 is hydrogen or alkyl; Appeal 2012-004990 Application 11/899,758 3 or R4 and R5 together form alkylene dioxy; R6 is hydrogen, lower alkyl, heteroalkyl, cycloalkyl, heterocyclylalkyl, or NR8R9; R10 is alkyl, cycloalkyl, heterocyclylalkyl, or NR8R9; R11 is alkyl, cycloalkyl, heteroalkyl, or (heterocyclyl)alkyl; R2 and R7 are each independently hydrogen, lower alkyl, hydroxyalkyl, or cycloalkyl; R8 is hydrogen, lower alkyl, or acyl; R9 is hydrogen, lower alkyl, heteroalkyl, aryl, heteroaryl, heterocyclyl, cycloalkyl; or R8 and R9 together with the nitrogen atom to which they are connected to form a heterocyclyl comprising at least one nitrogen ring atom, optionally substituted with OH, oxo, lower alkyl, lower alkoxy, or acyl; R12 is H, lower alkyl, cycloalkyl, -C(O)-R7, -SO2-Rll; each of m and x is independently an integer from 0 to 2;Y is hydrogen, - (CH2)n-OR7, -(CH2)n-C(O)-R7 or -(CH2)n-C(O)-OR7; each of y and z is independently 0 or 1; and n is an integer from 0 to 4. Claims 1-24 and 30 stand rejected under 35 U.S.C. § 103(a) as unpatentable over Gomper.2 ANALYSIS Gomper is directed to 2H-benzotriazole derivatives with electronic properties potentially useful in nonlinear optical devices. The Figure on page 14611 of the reference depicts the synthesis of six isomeric pairs of pyrimidinyl benzotriazoles in 1-H (meta) and 2-H (para) configurations. The Examiner finds that Gompers teaches a compound structurally analogous to one encompassed by claims 1-24 and 30. (Ans. 9.) In particular, the Examiner finds that Gomper’s compound 20b, a 1-H (meta) 2 Gomper et al., Chemistry and Nonlinear Optical Properties of New 2H- Benzotriazole Derivatives, 52 TETRAHEDRON (46):14607-14624 (1996). Appeal 2012-004990 Application 11/899,758 4 pyrimidinyl benzotriazole, differs from a claimed compound by having the benzotriazole attached to a different position on the pyrimidinyl ring, i.e., at the 4-position as compared to the 5-position of compound 20b. (Id.) This alteration can be visualized by rotating the benzotriazole moiety of compound 20b one position counter-clockwise around the pyrimidinyl ring, while retaining the meta configuration. The Examiner finds that compound 20b and the claimed compound are positional isomers, and notes that “‘[p]ositional isomerism has been used as a tool to obtain new and useful drugs,’” (Id. at 11, (citation omitted)) The Examiner further finds that one of ordinary skill in the art “would have been motivated to prepare the instantly claimed compounds because such isomeric compounds are suggestive of one another and would be expected to share similar properties and therefore, the same use as taught for the reference compounds, i.e., as synthetic agents having nonlinear optical properties.” (Id.) The Federal Circuit provides a two-prong analysis to determine whether a new chemical compound is prima facie obvious over particular prior art. The fact finder first determines whether a chemist of ordinary skill would have selected the asserted prior art compounds as lead compounds, or starting points, for further development efforts. (Otsuka Pharm. Co. v. Sandoz Inc., 678 F.3d 1280, 1291 (Fed. Cir. 2012). The Court defines a lead compound as “a compound in the prior art that would be most promising to modify in order to improve upon its ... activity and obtain a compound with better activity,” (Takeda Chem. Indus., Ltd. v. Alphapharm Pty., Ltd., 492 F.3d 1350, 1357 (Fed. Cir. 2007), or “a natural choice for further development efforts.” Altana Pharma AG v. Teva Pharm. USA, Inc., 566 Appeal 2012-004990 Application 11/899,758 5 F.3d 999, 1008 (Fed. Cir. 2009). The second step involves determining “whether the prior art would have supplied one of ordinary skill in the art with a reason or motivation to modify a lead compound to make the claimed compound with a reasonable expectation of success.” Otsuka, 678 F.3d at 1292 (citing Takeda, 492 F.3d at 1357). Following this two-step analysis, Appellants contend that the Examiner erred in failing to establish that one “one of ordinary skill in the art would have 1) selected the reference compound 20b as a lead compound for modification, or 2) modified the reference compound 20b at the 4- position and the 5-position on the pyrimidine to arrive at the claimed compounds.” (App. Br. 18.) Even if we accept the Examiner’s finding of compound 20b as a lead compound, we agree with Appellants with respect to the second prong of the analysis. In addressing the motivation to modify compound 20b, the Examiner relies on In re Duel, which states that: Structural relationships may provide the requisite motivation or suggestion to modify known compounds to obtain new compounds. For example, a prior art compound may suggest its homologs because homologs often have similar properties and therefore chemists of ordinary skill would ordinarily contemplate making them to try to obtain compounds with improved properties. Similarly, a known compound may suggest its analogs or isomers, either geometric isomers (cis v. trans) or position isomers (e.g., ortho v. para). In re Deuel (51 F.3d 1552, 1558 (Fed. Cir. 1995). The Examiner has not, however, shown how the structure of compound 20b suggested this particular isomer, nor evidence that one of ordinary skill in the art would have expected a counter-clockwise rotation of the benzotriazole moiety Appeal 2012-004990 Application 11/899,758 6 around the pyrimidinyl ring to produce similar, let alone improved, properties relative to the lead compound. Stated differently, A known compound may suggest its homolog, analog, or isomer because such compounds “often have similar properties and therefore chemists of ordinary skill would ordinarily contemplate making them to try to obtain compounds with improved properties.” . . . [H]owever, . . . in order to find a prima facie case of unpatentability in such instances, a showing that the “prior art would have suggested making the specific molecular modifications necessary to achieve the claimed invention” was also required. . . . Thus, in cases involving new chemical compounds, it remains necessary to identify some reason that would have led a chemist to modify a known compound in a particular manner to establish prima facie obviousness of a new claimed compound. Takeda, 492 F.3d at 1356-57 (citations omitted). As the Examiner has not pointed to sufficient reason to attempt this modification, we reverse. DECISION The rejection of claims 1-24 and 30 under 35 U.S.C. § 103(a) as unpatentable over Gomper is reversed. REVERSED lp