Ex Parte SchwinnDownload PDFBoard of Patent Appeals and InterferencesAug 6, 200910268969 (B.P.A.I. Aug. 6, 2009) Copy Citation UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE BOARD OF PATENT APPEALS AND INTERFERENCES __________ Ex parte DEBRA A. SCHWINN __________ Appeal 2009-004912 Application 10/268,969 Technology Center 1600 __________ Decided: August 7, 2009 __________ Before DEMETRA J. MILLS, RICHARD M. LEBOVITZ, and STEPHEN WALSH, Administrative Patent Judges. WALSH, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134(a) involving claims to a method of treating bladder symptoms. The Patent Examiner rejected the claims for lacking descriptive and enabling support. We have jurisdiction under 35 U.S.C. § 6(b). We affirm-in-part. Appeal 2009-004912 Application 10/268,969 STATEMENT OF THE CASE According to the Specification, the invention “is based on the recognition of α1d[-adrenergic receptor or AR] as the α1AR subtype responsible for irritative symptoms associated with bladder and lower urinary tract diseases.” (Spec. 6:12-14.) “The method of treatment to which the invention relates comprises administering to a patient suffering irritative symptoms an amount of an α1dAR antagonist sufficient to relieve such symptoms.” (Id. at 18-20.) Claims 1-10, which are all the pending claims, are on appeal. Claims 1 and 9 are representative and read as follows: 1. A method of treating irritative symptoms of bladder or lower urinary tract disease comprising administering to a patient in need of such treatment an amount of an α1d-adrenergic receptor (α1dAR) antagonist sufficient to effect said treatment. 9. A method of treating irritative symptoms of bladder or lower urinary tract disease comprising administering to a patient in need of such treatment an effective amount of a construct comprising an oligonucleotide that inhibits production of α1dAR or that encodes a molecule that inhibits production of α1dAR. The Examiner relied on the following evidence: Dwaine A. Braasch et al., Novel Antisense and Peptiode Nucleic Acid Strategies for Controlling Gene Expression, 41 BIOCHEM. 4503-10 (2002). Alan M. Gewirtz et al., Facilitating oligonucleotide delivery: Helping antisense deliver on its promise, 93 PROC. NATL. ACAD. SCI. USA 3161-63 (1996). Sudhir Agrawal, Antisense oligonucleotides: towards clinical trials, 14 TIBTECH 376-87 (1996). Andrea D. Branch, A good antisense molecule is hard to find, 23 TIBS 45- 50 (1998). 2 Appeal 2009-004912 Application 10/268,969 Ingo Tamm et al., Antisense therapy in oncology: new hope for an old idea?, 358 THE LANCET 489-97 (2001). The Examiner rejected the claims as follows: • claims 1-8 under 35 U.S.C. § 112, ¶ 1, for lack of compliance with the written description requirement, i.e., for failure to provide descriptive support for the scope of the genus “antagonist” used in the claimed method; and • claims 1-10 under 35 U.S.C. § 112, ¶ 1, for lack of compliance with the enablement requirement, i.e., for failure to enable in vivo treatment with inhibitor oligonucleotide constructs. WRITTEN DESCRIPTION The Written Description Issue The Examiner found that the claims are directed to methods of using any agent that acts as an antagonist to the α1dAR, and that such a genus would include any small molecule inhibitor of α1dAR, a variety of oligonucleotide therapeutics, peptide inhibitors, and antibodies. (Ans. 4.) The Examiner found that the Specification did not describe such a broad genus, and that the Specification’s disclosure of one known small molecule inhibitor, Prazosin, and a cDNA sequence corresponding to α1dAR did not provide a representative sample of structures describing the broad genus. (Id. at 5.) According to the Examiner, Applicants may not patent “an invention that is not considered to be in their possession at the time of filing.” (Id. at 4-5.) Appellant contends that the “[A]pplication makes it clear that, at the time of filing, Appellant had possession of a variety of types of α1dAR 3 Appeal 2009-004912 Application 10/268,969 antagonists suitable for use in treating irritative symptoms.” (App. Br. 10.)1 “Further, the disclosure includes an extensive discussion of assays that could be used to identify small molecule antagonists.” (Id.) Appellant disputes the Examiner’s reliance on the Rochester case, arguing that the active agent in the claims here “is not defined by the effect sought.” (Id. at 11.) The issues with respect to this rejection are: did the Specification describe as broad a variety of antagonists as claimed; did the disclosure of assays for identifying antagonists describe the antagonists; do the claims define the antagonist used in the claimed method by the effect sought? Findings of Fact 1. The claimed method includes a step administering “an α1d-adrenergic receptor (α1dAR) antagonist.” (Claim 1.) 2. “[A]n α1d-adrenergic receptor (α1dAR) antagonist” denotes a genus of compounds. 3. The Specification does not explicitly define the compounds in the genus. 4. The Examiner found that the genus “antagonist” includes “any small molecule inhibitor of α1dAR, . . . other peptide inhibitors, and antibodies.” (Ans. 4.) 1 Citations are to the “Amended Appeal Brief” filed April 25, 2008. 4 Appeal 2009-004912 Application 10/268,969 5. The Specification mentions the known AR antagonist prazosin. (Spec. 3:22.) 6. The Specification mentions the known radiolabeled AR antagonist [125I]HEAT. (Id. at 5:7-13.) 7. The Specification mentions the selective ligand BMY7378 but does not identify it as an AR antagonist. (Id. at 6:7-8.) 8. The Specification indicates that a compound found to bind in a screening assay is “potentially” an antagonist. (Id. at 7:5-7.) 9. “To determine the specific effect of any particular test compound selected on the basis of its ability to bind α1dAR, various assays can be used including IP assays . . . and bladder (e.g. human bladder) smooth muscle contraction assays . . . .” (Id. at 10:18-22.) 10. “Compounds suitable for use in treating irritative symptoms will be associated with antagonistic (inhibitory) effects in the IP assay and contraction inhibitory effects in the contraction assay.” (Id. at 22-24.) 11. Antibodies specific for α1dAR “can be formulated as pharmaceutical compositions and used therapeutically as α1dAR antagonists.” (Id. at 11:13-15.) 12. The Specification discloses that α1dAR oligonucleotide and antisense constructs can be used to treat irritative symptoms. (Id. at 16-24.) Principles of Law Relating to Written Description When an Applicant claims a class of compounds or materials, the Applicant “must describe that class in order to meet the description requirement of the statute.” In re Lukach, 442 F.2d 967, 968 (CCPA 1971). A description of what a material does, rather than of what it is, usually does 5 Appeal 2009-004912 Application 10/268,969 not suffice. Regents of the Univ. of Cal. v. Eli Lilly & Co., 119 F.3d 1559, 1568 (Fed. Cir. 1997). Regardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to that subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods. Univ. Of Rochester v. G.D. Searle & Co., Inc., 358 F.3d 916, 926 (Fed. Cir. 2004). “[W]here no explicit description of a generic invention is to be found in the specification . . . mention of representative compounds may provide an implicit description upon which to base generic claim language.” In re Robins, 429 F.2d 452, 456-57 (CCPA 1970). Analysis of the Written Description Issue As to Appellant’s first issue, the evidence of record is that Appellant had possession of the antagonists Prazosin, [125I]HEAT, and a cDNA corresponding to α1dAR at the time of filing. The Specification did not provide an explicit definition of the genus “α1dAR antagonist,” and Appellant does not dispute the Examiner’s finding that the genus α1dAR antagonist necessarily includes other small molecules, peptides, antibodies, and other molecules, none of which were named or described. Appellant offers no evidence that a person of skill in the art would credit Prazosin, [125I]HEAT, and the one disclosed cDNA as describing the genus α1dAR antagonist. A written description of the genus of compositions to be used in a method could be achieved by (i) a description of a representative number of 6 Appeal 2009-004912 Application 10/268,969 compositions falling within the genus, or (ii) a recitation of distinguishing structural features common to members of the genus, which features constitute a substantial portion of the genus. See e.g., Eli Lilly, 119 F.3d at 1568 (“A written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials.”). Although the statute does not require representative species, “where no explicit description of a generic invention is to be found in the specification . . . mention of representative compounds may provide an implicit description upon which to base generic claim language.” Robins, 429 F.2d at 456-57. In other words, representative species “are a means by which certain requirements of the statute may be satisfied.” Id. A representative number of species could be described by a “disclosure of sufficiently detailed, relevant identifying characteristics,” such as “complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics.” Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 964 (Fed. Cir. 2002). Thus, an additional way to describe a genus could be (iii) reliance on a known or disclosed correlation between function and structure. See e.g., Amgen, Inc. v. Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1332 (Fed. Cir. 2003) (“the requirement may be satisfied if in the knowledge of the art the disclosed function is sufficiently correlated to a particular, known structure”). Appellant offered no evidence or explanation that the disclosure met any of these tests, or that it described the 7 Appeal 2009-004912 Application 10/268,969 genus in another way. Finding no explicit or implicit description of the genus, we agree with the Examiner that the genus of antagonists to be used in the method was not described. As a second issue, Appellant argues that the disclosure of assays for identifying antagonists sufficed to describe antagonists that would be identified. We disagree. The assays test compounds in two stages. (FF8- 10.) A first assay determines if a compound binds the receptor as a “potential” antagonist, and a second assay determines if a potential antagonist identified in the first assay actually inhibits (i.e., antagonizes) in a biological assay. Until a compound passes both tests, it is unknown whether the test compound is an antagonist. Appellant offers no evidence that a person of skill in the art would accept the Specification’s description of the two-stage assay as descriptive of the genus of antagonists to be used in the method of treatment. We find that Appellant was not in possession of the genus at the time the Application was filed. “This is exactly the type of overreaching the written description requirement was designed to guard against.” Purdue Pharma L.P. v. Faulding Inc., 230 F.3d 1320, 1327 (Fed. Cir. 2000). Like the Examiner, we find Rochester determinative here and we are not persuaded by Appellant’s third argument. Appellant argues that Rochester is inapt because the antagonists to be used in Appellant’s method are not defined by the effect sought. (App. Br. 11.) That is, the effect sought in Appellant’s claims is “treating,” and the compound to be used is not defined in terms of the “treating” effect. (Id.) Instead, the compound to be used is “an α1d-adrenergic receptor (α1dAR) antagonist.” (Id.) We find this distinction makes no real difference because the word “antagonist” has 8 Appeal 2009-004912 Application 10/268,969 only a functional meaning in claim 1 as something that antagonizes or inhibits the receptor. The functional word does not serve to define the genus because it does not distinguish the genus from other molecules except by function. See Eli Lilly, 119 F.3d at 1568. One skilled in the art cannot visualize or recognize the identity of other members of the genus. Naming a type of material which may or may not exist, in the absence of knowledge as to what that material consists of, is not a description of that material. Id.; accord, Holland Furniture Co. v. Perkins Glue Co., 277 U.S. 245, 257-58 (1928) (“the attempt to broaden product claims by describing the product exclusively in terms of its use or function is subject to the same vice as is the attempt to describe a patentable device or machine in terms of its function”). Finally, Appellant did not disclose a correlation between the function of antagonizing α1dAR and the structure of the broad class “antagonist,” other than for antisense oligonucleotides. Claims 9 and 10 use nucleic acid molecules, and are not subject to this rejection. The oligonucleotide antagonists are disclosed to function by inhibiting production of α1dAR or encoding a molecule that inhibits production of α1dAR. Appellant does not offer any evidence that those of ordinary skill in the art would accept the oligonucleotide disclosure as descriptive of the broader antagonist class to be used in claim 1. If there was any pre-existing knowledge in the art of a relevant correlation that could have supplemented the Specification’s deficiency, Appellant provided no evidence of it, e.g., correlating antisense oligonucleotides to other kinds of inhibitors. There is nothing in the record establishing that those of skill in the art would have understood Appellant’s oligonucleotide disclosure to correlate to possession of methods using other kinds of antagonists. 9 Appeal 2009-004912 Application 10/268,969 As in Rochester, the claims are directed to a process for accomplishing a desired result using a composition having a specified functional property. Here the generic phrase “α1dAR antagonist” does not define structural features of the compounds that distinguish them from other compounds. Claims 2-8 were not been argued separately and therefore fall with claim 1. 37 C.F.R. § 41.37(c)(1)(vii). ENABLEMENT The Enablement Issue The Examiner’s position is that the Specification “does not provide sufficient guidance or appropriate examples that would enable a skilled artisan to use the disclosed [oligonucleotide] compounds or methods of using said compounds in in vivo environments.” (Ans. 6.) The Examiner found that the state of antisense treatment, as evidenced by five articles in the scientific literature, was that (1) predicting inhibitory activity of an antisense molecule was difficult, (2) uptake of oligonucleotides into target cells was not likely to be efficient, (3) non-antisense effects, such as undesireable immunostimulatory activity, were unpredictable, (4) it was challenging to obtain a therapeutic effect, and (5) there was a likelihood that in vitro studies would not always predict in vivo efficacy. (Id. at 7-10.) The Examiner found the Specification’s prophetic examples gave insufficient guidance to resolve the unpredictable areas, and concluded that the claimed method was not enabled. (Id. at 13-14.) Appellant contends that (i) exemplification is not required to satisfy the enablement requirement, and (ii) the publications the Examiner relied on 10 Appeal 2009-004912 Application 10/268,969 “are not related to treatment of irritative symptoms associated with bladder and lower urinary tract diseases.” (App. Br. 12, emphasis omitted.) The issues with respect to this rejection are: did the Examiner require examples; and did the publications establish a reason to doubt the Specification was enabling? Findings of Fact 13. The Specification instructs that oligonucleotide or antisense constructs can be delivered “using any of a variety of approaches,” including instillation into the bladder, systemically, via viral vectors, or via liposomes. (Spec. 12:1-10.) 14. According to the Specification, “[o]ne skilled in the relevant art can readily optimize the dose and treatment regimen.” (Id. at 10-13.) 15. According to Braasch, “[i]n practice over the last decade . . . gene inhibition by antisense oligomers has not proven to be a robust or generally reliable technology.” (4503, ¶ 1.) 16. Braasch reports that more recent results with Fomivirsen, Genasense, and ISIS 3521 “are encouraging because they indicate that oligonucleotides can enter human tumors in vivo and have a favorable impact on disease progression.” (4506, left col.) 17. Braasch further writes that “[s]ince the pharmacokinetic properties of oligonucleotides are likely to be similar regardless of oligonucleotide sequence, progress in the Genasense and ISIS 3521 trials encourages the belief that it will be possible to target many other genes successfully.” (Id.) 11 Appeal 2009-004912 Application 10/268,969 18. Braasch reports that “[e]xperience in the clinic is demonstrating that even older generation oligonucleotide designs are effective drugs . . . .” (4509, last para.) 19. Gewirtz reports that antisense technology “has been found to be highly variable in its efficiency.” (3161, middle col.) 20. According to Agrawal, “[t]he specificity and application of antisense oligonucleotides have been strongly validated in animal models for various disease targets.” (Abstract.) 21. Tamm reports that “[o]ne antisense drug has been approved for local treatment of cytomegalovirus-induced retinitis, and several antisense oligonucleotides are in clinical trials, including oligonucleotides that target the mRNA of BCL2, protein-kinase-C alpha, and RAF kinase.” (Abstract.) 22. According to Tamm, “[v]arious other targets in the field of oncology have been analysed in vitro and in animals . . . with encouraging results (panel 1).” (490, left col.) 23. Tamm reports that “[t]he number of clinical trials ongoing represents a growing interest in antisense technology (panel 2).” (490, right col.) 24. According to Tamm, “results suggest that the principle of antisense works, not only with local treatment, as shown with fomivirsen, but also with systematic treatment with antisense oligonucleotides.” (495, left col.) 25. Branch reports that “[t]he time and expense necessary to screen large numbers of potential antisense molecules and ribozymes, and to carefully monitor their in vivo effects, raise the stakes for those seeking to use them as genetic probes.” (50, left col.) 12 Appeal 2009-004912 Application 10/268,969 26. According to Branch, “there is growing evidence that antisense molecules can be useful pharmacological tools when applied carefully.” (Id.) Principles of Law Relating to Enablement The first paragraph of 35 U.S.C. § 112 requires that the specification teach persons skilled in the art to make and use the invention without undue experimentation. In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988). A lack of enablement rejection is appropriate where the written description fails to teach those in the art to make and use the invention as broadly as claimed without undue experimentation. In re Cortright, 165 F.3d 1353, 1356 (Fed. Cir. 1999). “The PTO cannot make this type of rejection, however, unless it has reason to doubt the objective truth of the statements contained in the written description.” Id. at 1357. Analysis of the Enablement Issue Appellant’s first argument relating to the enablement issue is that “exemplification is not required.” (App. Br. 12.) The Examiner pointed to the lack of examples as “a legitimate factor in determining lack of enablement, especially when the art is of an unpredictable nature,” citing In re Wands. (Ans. 13.) We agree that the presence or absence of examples is a legitimate factor for consideration with respect to enablement. We understand the Examiner’s explanation of deficiencies in the disclosure are not a requirement for examples, but are an observation that examples might have filled the gaps the Examiner perceived. Appellant’s first argument does not help to resolve whether the Examiner appropriately weighed the available evidence. 13 Appeal 2009-004912 Application 10/268,969 Appellant’s second argument is that the publications the Examiner relied on are not related to treating bladder symptoms. (App. Br. 12.) The publications concern experience with antisense therapy generally. All five publications indicate that antisense therapy works, albeit not efficiently, and they discuss various challenges in achieving success. (FF1-12.) The Examiner focused on the difficulties mentioned in the publications. We agree that the publications proffered by the Examiner, while not directly related to treating bladder symptoms, do relate more broadly to the administration of antisense compounds within the scope of the claim and establish that this art requires much screening and careful monitoring. (FF25.) However, Appellant provided the cDNA sequence needed for making antisense molecules. We are not persuaded that screening candidate antisense molecules from the cDNA sequence disclosed, and carefully monitoring their performance, would be undue experimentation in this field. The literature indicates this is the nature of the art, and that careful monitoring is required. See Wands, 858 F.2d at 740 (screening many hybridomas to find useful ones was not undue experimentation in that art). CONCLUSIONS OF LAW Written Description The Specification did not explicitly or implicitly describe the genus of antagonists to be used as claimed; the disclosure of assays for identifying antagonists did not describe the antagonists; and claims 1-8 define the antagonist to be used in the claimed method by the function of antagonizing or inhibiting, i.e., by an effect sought. 14 Appeal 2009-004912 Application 10/268,969 Enablement The Examiner did not issue a requirement for examples; and the publications did not establish a reason to doubt the Specification was enabling. SUMMARY We affirm the rejection of claims 1-8 under 35 U.S.C. § 112, ¶ 1, for lack of compliance with the written description requirement; and we reverse the rejection of claims 1-10 under 35 U.S.C. § 112, ¶ 1, for lack of compliance with the enablement requirement. 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-IN-PART cdc NIXON & VANDERHYE, PC 901 NORTH GLEBE ROAD, 11TH FLOOR ARLINGTON VA 22203 15 Copy with citationCopy as parenthetical citation