Ex Parte Terrero

Patent Trial and Appeal BoardApr 12, 2013

11139338 (P.T.A.B. Apr. 12, 2013)

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. 11/139,338 05/26/2005 David Terrero MAGNA 100 CON 2878 23579 7590 04/15/2013 Pabst Patent Group LLP 1545 PEACHTREE STREET NE SUITE 320 ATLANTA, GA 30309 EXAMINER CHANDRAKUMAR, NIZAL S ART UNIT PAPER NUMBER 1625 MAIL DATE DELIVERY MODE 04/15/2013 PAPER 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. PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE PATENT TRIAL AND APPEAL BOARD __________ Ex parte DAVID TERRERO __________ Appeal 2011-011722 Application 11/139,338 Technology Center 1600 __________ Before ERIC GRIMES, FRANCISCO C. PRATS, and STEPHEN WALSH, Administrative Patent Judges. PRATS, Administrative Patent Judge. DECISION ON APPEAL This appeal under 35 U.S.C. § 134 involves claims to pharmaceutical compositions. The Examiner entered a rejection for lack of written description, and a rejection for lack of enablement. We have jurisdiction under 35 U.S.C. § 6(b). We reverse the rejection for lack of written description, but affirm the rejection for lack of enablement. STATEMENT OF THE CASE Claims 1, 3, 4, 6, and 32-41 stand rejected and appealed (App. Br. 2). Claims 1, 3, 4, and 6 illustrate the appealed subject matter and read as follows: Appeal 2011-011722 Application 11/139,338 2 1. A pharmaceutical composition comprising a compound having Formula Ic: wherein R1-R9 are independently selected from the group consisting of hydrogen atom or any other groups or groupings selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, halo, hydroxyl, alkoxy, substituted alkoxy, phenoxy, substituted phenoxy, aroxy, substituted aroxy, alkylthio, substituted alkylthio, phenylthio, substituted phenylthio, arylthio, substituted arylthio, cyano, isocyano, substituted isocyano, carbonyl, substituted carbonyl, carboxyl, amino, substituted amino, amido, substituted amido, sulfonyl, substituted sulfonyl, sulfonic acid, phosphoryl, substituted phosphoryl, phosphonyl, substituted phosphonyl, polyaryl, substituted polyaryl, C1-C20 cyclic, substituted C1-C20 cyclic, heterocyclic, substituted heterocyclic, aminoacid, peptide, and polypeptide groups, or R5 and R6 taken together form a cyclic structure selected from the group consisting of aryl, substituted aryl, heteroaryl, substituted heteroaryl, aroxy, substituted aroxy, arylthio, substituted arylthio, C1-C20 cyclic, substituted C1-C20 cyclic, heterocyclic, and substituted heterocyclic; Y1, Y2, and Y3 are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, halo, hydroxyl, Appeal 2011-011722 Application 11/139,338 3 alkoxy, substituted alkoxy, phenoxy, substituted phenoxy, aroxy, substituted aroxy, alkylthio, substituted alkylthio, phenylthio, substituted phenylthio, arylthio, substituted arylthio, cyano, isocyano, substituted isocyano, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, sulfonyl, substituted sulfonyl, sulfonic acid, phosphoryl, substituted phosphoryl, phosphonyl, substituted phosphonyl, polyaryl, substituted polyaryl, Cl-C20 cyclic, substituted Cl-C20 cyclic, heterocyclic, substituted heterocyclic, aminoacid, peptide, and polypeptide groups, or Y1 and Y2 taken together form a cyclic structure selected from the group consisting of aryl, substituted aryl, heteroaryl, substituted heteroaryl, aroxy, substituted aroxy, arylthio, substituted arylthio, C1-C20 cyclic, substituted C1-C20 cyclic, heterocyclic, and substituted heterocyclic; Z is a heteratom selected from the group consisting of oxygen, sulfur, and nitrogen; and X is a heteratom selected from the group consisting of oxygen, sulfur, and nitrogen; and a pharmaceutically acceptable carrier for parenteral, enteral, or topical administration. 3. The composition of claim 1 wherein the X is an oxygen. 4. The composition of claim 1 wherein where R1 and R2 are hydrogen. 6. The composition of claim 1, wherein the compound is: . Appeal 2011-011722 Application 11/139,338 4 The following rejections are before us for review: (1) Claims 1, 3, 4, 6, and 32-41, under 35 U.S.C. § 112, first paragraph, as failing to comply with the written description requirement (Ans. 4-5); and (2) Claims 1, 3, 4, 6, and 32-41, under 35 U.S.C. § 112, first paragraph, as failing to comply with the enablement requirement (Ans. 5- 13). WRITTEN DESCRIPTION The Examiner found that, while the “claimed inventions relate to trillions of natural product[-]like complex sesquiterpene derivatives” the relevant underlying disclosure in the Specification “is limited to a drawing of single structural formula (4') on page 7 of the specification” (Ans. 4-5). The Examiner thus reasoned: Though possession may be shown by clear depiction of the invention in detailed drawing or in structural chemical formulas, a fact-based inquiry in this case would lead one of skill in the art to recognize that the description by drawing of a structure of a molecule is inadequate to conclude that the appellant had possession of any compound that fall[s] under the claimed formula. (Id. at 5.) As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992): [T]he examiner bears the initial burden . . . of presenting a prima facie case of unpatentability. . . . After evidence or argument is submitted by the applicant in response, patentability is determined on the totality of the record, by a preponderance of evidence with due consideration to persuasiveness of argument. Appeal 2011-011722 Application 11/139,338 5 To meet the initial burden of establishing a prima facie case of unpatentability based on the written description requirement, the Examiner must “„present[] evidence or reasons why persons skilled in the art would not recognize in the disclosure a description of the invention defined by the claims.‟” In re Alton, 76 F.3d 1168, 1175 (Fed. Cir. 1996). As discussed below in the context of enablement, we agree with the Examiner that the Specification does not describe any specific processes for making the compounds recited in the claims. As our reviewing court has explained, however, “the written description requirement does not demand either examples or an actual reduction to practice; a constructive reduction to practice that in a definite way identifies the claimed invention can satisfy the written description requirement.” Ariad Pharmaceuticals, Inc. v. Eli Lilly and Co., 598 F.3d 1336, 1352 (Fed. Cir. 2010) (citing Falkner v. Inglis, 448 F.3d 1357, 1366- 67 (Fed. Cir. 2006)). As Appellant argues, and the Examiner does not dispute, the Specification includes formulae that describe each and every compound recited in the claimed compositions (see Spec. 5-7). Moreover, the Examiner points to no clear or specific evidence suggesting that an ordinary artisan viewing the Specification would fail to understand the scope of the claimed subject matter. Thus, as the Specification provides a disclosure that positively identifies, in a definite way, the compounds Appellant considers to be the claimed invention, we agree with Appellant that the preponderance of the evidence does not support the Examiner‟s finding that the claims lack Appeal 2011-011722 Application 11/139,338 6 adequate descriptive support. We therefore reverse the Examiner‟s rejection for lack of written description. ENABLEMENT The Examiner found that the disclosure in the Specification regarding the compounds recited in the claims “is limited to a drawing of a molecular structure of a species of the claimed genus” (Ans. 5-6 (citing Spec. 7)). In particular, the Examiner found: There is no disclosure in the specification of how to make or use this molecule or any other molecule that would fall under the formula of the claimed genus. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims. (Id. at 6.) The Examiner noted that, because the claimed compounds include “substituents layered on top of substituents[,] the number of conceivable compounds encompassed by the formula [of claim 1] is large” (id. at 7). The Examiner contrasted the broad claim scope with the single compound produced in the working examples, which “bears little structural similarity to that of the instantly claimed materials” (id.). Given the Specification‟s failure to describe any specific steps by which a skilled artisan could arrive at the claimed compounds from the single exemplified compound, the Examiner reasoned that the artisan “would need to design and execute a complicated multistep synthesis: Appeal 2011-011722 Application 11/139,338 7 The design and execution of such a synthesis is undue experimentation” (id. at 8 (citing Dorwald 1 as evidence of unpredictability in the art)). The Examiner also found that the Specification‟s disclosure “with respect to potential use aspect of the enablement requirement is found on pages 17-28 wherein the biological activity of compound of Example-1 . . . is disclosed” (id. at 11). The Examiner reasoned that a skilled artisan “would not anticipate the biological properties of Example-1 to represent the biological activity of instantly claimed compounds such [as] . Such an anticipation would defy art recognized concepts of structure-activity relationship” (id. at 11-12). 1 FLORENCIO ZARAGOZA DÖRWALD, SIDE REACTIONS IN ORGANIC SYNTHESIS, A GUIDE TO SUCCESSFUL SYNTHESIS DESIGN (WILEY-VCH 2005). Appeal 2011-011722 Application 11/139,338 8 Appellant argues that the “fact that experimentation may be complex does not necessarily make it undue, if the art typically engages in such experimentation” (App. Br. 15). Thus, Appellant argues, the test is not “merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides reasonable amount of guidance with respect to the direction in which the experimentation should proceed to enable determination of how to practice desired embodiment of invention claimed” (id.). As to the field of endeavor with which the instant application is concerned, Appellant argues: Complex natural product and natural product-inspired molecules are synthesized regularly, and published in a multitude of peer-reviewed journals, in spite of the Examiner‟s alleged onerous effort. Like all science, organic synthesis requires trial and error to identify the contributing factors towards undesired decomposition, reactivity, etc. An entire field of organic synthesis, methodology, is aimed at identifying routes to explain and circumvent such problems with new reagents, reaction conditions, and purification conditions. The fact that organic synthesis is labor-intensive and often has pitfalls does not mean that undue experimentation is required to attain a successful synthetic route. (Id. at 18.) In particular, Appellant argues that Dorwald “serves to highlight the high level of experimentation ordinarily required within the field of the invention” (id. at 19). Appellant urges that the Specification provides four successful synthetic methodologies for providing lactones of the type recited in claims 1, 3, 4, and 6, and the working examples demonstrate the biological activity of a compound that would be indicative of the activity of the claimed Appeal 2011-011722 Application 11/139,338 9 compounds (see id. at 19-20). Appellant further argues that the Schuster reference 2 describes a compound with a core structure very similar to that of the claimed compounds, and provides the following comparison as evidence that Schuster‟s compound differs from the claimed genus in that Schuster‟s compound contains an exocyclic ketone (id. at 21): Appellant argues that, as shown by the BASF reference, 3 which in turn cites references alleged as being prior art to the rejected claims, “methods for the selective reduction of ketones in the presence of lactones were known in the art” (id.). Additionally, Appellant argues, as shown by the Hoffmann reference, 4 “the synthesis and biosynthesis of complex α- methylene γ-lactone derivatives is known in the art” (id. at 22). 2 A. Schuster et al., Sesquiterpene Lactones from Koanophyllon Albicaule, 31 PHYTOCHEMISTRY 3143-3146 (1992). 3 BASF product description entitled Boron Reagents For Selective Reduction (submitted/cited in the Response filed January 18, 2010 (publication date unknown) (see App. Br. 28 (Evidence Appendix)). 4 H.M.R. Hoffmann and Jürgen Rabe, Synthesis and Biological Activity of α-Methylene-γ-butyrolactones, 24 ANGEW. CHEM. INT. ED. ENGL. 94-110 (1985). Appeal 2011-011722 Application 11/139,338 10 Thus, Appellant concludes: One skilled in the art will recognize that selection of the appropriate route for synthesis of a given analogue depends on the structure of the analogue as a whole as it relates to compatibility of functional groups, protecting group strategies, and the presence of labile bonds. However, the breadth of synthetic possibilities and the complex structures yielded by these synthetic routes illustrates the current level of skill in the art is such that synthesis of compounds of Formula Ic can be performed by one skilled in the art without undue experimentation. (Id. at 22.) Appellant‟s arguments do not persuade us that a preponderance of the evidence fails to support the Examiner‟s conclusion of non-enablement. While claim 1 limits the compounds included in the claimed composition to those encompassed by formula Ic, formula Ic includes fourteen substituents which can have variable moieties: R1-R9, Y1-Y3, X, and Z. While claim 1 limits substituents X and Z to oxygen, sulfur, and nitrogen, claim 1 provides that substituents R1-R9 and Y1-Y3 can each be any one of about 65 different classes of chemical groups, each of which (“alkyl,” “substituted alkyl,” etc.) encompasses a large number of different moieties. Thus, claim 1 recites compounds with twelve different positions that can each be substituted with a large number of chemical moieties chosen from any of about 65 different classes of organic groups. While claim 3 limits the X substituent of claim 1 to oxygen, claim 3 does not otherwise change this high degree of variability. Similarly, while claim 4 limits the R1 and R2 substituents to hydrogen, the remaining ten highly variable positions, R3-R9 and Y1-Y3, may all still be substituted with any moiety chosen from any of about 65 different classes of organic groups. Appeal 2011-011722 Application 11/139,338 11 We thus agree with the Examiner that the scope of the subject matter recited claims 1, 3, and 4 is fairly vast. We also agree with the Examiner that the Specification simply does not explain, with any specificity, how any of the compounds encompassed by claims 1, 3, or 4 may be prepared, nor does the Specification explain how the compound recited in claim 6 may be prepared. Specifically, Example 1 is the sole working example in which compounds are produced. Example 1 produces the compound “LMSV-6 (Securolide TM )” from Securidaca virgata roots by a solvent extraction method (see Spec. 15). Example 1 explains that Securolide TM is designated as compound (1) (id. at 16). Example 1 also describes obtaining compound (2) from fractions of the extract (see id.). As the Specification explains, compound (1), also referred to as securolide, Securolide TM , and LMSV-6, has the following structure (see id. at 6-7): As the Specification also explains, compound 2 has the following structure (id. at 7): Appeal 2011-011722 Application 11/139,338 12 In the remaining examples, the Specification describes tests which demonstrate the antibacterial, antiproliferative, and antifungal activities of Securolide TM , and its attendant utility in treating periodontal disease (see Spec. 17-28). The Specification does not describe testing the biological activities of any compound other than Securolide TM (see id.). We note that the Specification provides several lactone synthesis schemes (see id. at 8-12). As is evident, however, those schemes do not describe syntheses that result in compounds encompassed by formula Ic, but instead produce a compound similar to Securolide TM (compare lactone (4) on pages 9, 10, and 12 of Specification to Securolide compound (1) at page 6), as well as simple derivatives of that compound (see id. at 8-12). We also note the Specification‟s assertion that “[m]ore functionalized lactones can be prepared by readily available synthetic method in the art (see, for example, March, „Advanced Organic Chemistry,‟ 4th Edition, 1992, Wiley-Interscience Publication, New York)” (id. at 11). This reference to an organic chemistry textbook does not, however, provide or outline, with any specificity, any synthetic schemes by which an ordinary artisan might arrive at even one of the many compounds recited in claims 1, 3, and 4, or the single compound recited in claim 6. As to the how-to-use element of the enablement requirement, as the Examiner pointed out, the sole compound for which any biological activity is shown is the Securolide TM compound, which is not encompassed by formula Ic, and has a significantly different structure than the compounds recited in claims 1, 3, 4, and 6. Appeal 2011-011722 Application 11/139,338 13 Thus, given the scope of claims 1, 3, and 4, and given the absence of any clear or specific synthetic scheme in the Specification explaining to a skilled practitioner how to make the compounds recited in claims 1, 3, or 4, or claim 6 for that matter, and given Dorwald‟s disclosure of the high level of difficulty and unpredictability in organic syntheses (see Dorwald, Preface), and further given the absence of any disclosure in the Specification that any of the compounds in claims 1, 3, 4, and 6 has any biological activity, we agree with the Examiner that an ordinary artisan would have expected that making and using the full scope of claims 1, 3, 4, and 6 would require undue experimentation. We are therefore not persuaded that the Examiner failed to make out a prima facie case of lack of enablement. We acknowledge Schuster‟s disclosure that a compound with a similar core structure to the compounds recited in claims 1, 3, 4, and 6 can be isolated from plant tissue (see Schuster 3144 (structure 8)). We also acknowledge the BASF reference‟s disclosure of boron reagents useful in ketone reduction (see BASF generally). The compounds recited in claims 1, 3, and 4, however, include numerous different substituents not mentioned in either Schuster or BASF, and Appellant has not adequately explained how one could arrive at those compounds from the compound described in Schuster through ketone reduction. Similarly, while claim 6 recites a single compound, that compound differs from Schuster‟s compound 8 not only in the presence of an exocyclic ketone at position Y1, but also in having hydroxyl groups at positions Y2 and Y3, both of which are unsubstituted in Schuster‟s compound. The compound of claim 6 also differs from Schuster‟s compound 8 at positions R6 and R9 of formula Ic. Appeal 2011-011722 Application 11/139,338 14 Appellant has not explained how, despite those differences, one would arrive at claim 6‟s compound from Schuster‟s compound, even with the knowledge imparted by the BASF reference. Moreover, the Specification simply does not mention Schuster as providing the starting compounds for preparing any of the compounds of formula Ic encompassed by claims 1, 3, 4, and 6. We further acknowledge Hoffmann‟s disclosure of synthetic schemes that might be used to prepare compounds similar to those recited in claims 1, 3, 4, and 6 (see Hoffmann generally). Again, however, Appellant does not point to any disclosure, in the Specification or in the prior art, of any compound which is asserted to be a starting material from which the compounds recited in claims 1, 3, 4, and 6 may be prepared, nor does Appellant point to any specific synthetic scheme or series of steps that may be used to prepare those compounds. We are therefore not persuaded that the Examiner erred in maintaining the rejection for lack of enablement. As our reviewing court has explained, while the Specification need not disclose what is well known in the art, “that general, oft-repeated statement is merely a rule of supplementation, not a substitute for a basic enabling disclosure. It means that the omission of minor details does not cause a specification to fail to meet the enablement requirement.” Genentech, Inc. v. Novo Nordisk A/S, 108 F.3d 1361, 1366 (Fed. Cir. 1997) (citation omitted). In contrast, as is the case here, when there is no disclosure of any specific starting material or of any of the conditions under which a process can be carried out, undue experimentation is required; there is a failure to meet the enablement requirement that cannot be rectified by asserting Appeal 2011-011722 Application 11/139,338 15 that all the disclosure related to the process is within the skill of the art. It is the specification, not the knowledge of one skilled in the art, that must supply the novel aspects of an invention in order to constitute adequate enablement. This specification provides only a starting point, a direction for further research. Id. In sum, as we agree with the Examiner, for the reasons discussed, that the Specification fails to adequately enable methods of making and using the compositions recited in claims 1, 3, 4, and 6, we affirm the Examiner‟s enablement rejection of those claims. As they were not argued separately, claims 32-41 fall with those claims. See 37 C.F.R. § 41.37(c)(1)(vii). SUMMARY We reverse the Examiner‟s rejection of claims 1, 3, 4, 6, and 32-41, for failure to comply with the written description requirement. We affirm the Examiner‟s rejection of claims 1, 3, 4, 6, and 32-41 for failure to comply with the enablement requirement. TIME PERIOD No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a). AFFIRMED cdc