Ex Parte Xu et al

Patent Trial and Appeal BoardSep 18, 2012

11289723 (P.T.A.B. Sep. 18, 2012)

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. 11/289,723 11/30/2005 Weiming Xu 9516-339-999 (501872-331) 5356 20582 7590 09/18/2012 JONES DAY 222 East 41st Street New York, NY 10017-6702 EXAMINER THOMAS, TIMOTHY P ART UNIT PAPER NUMBER 1628 MAIL DATE DELIVERY MODE 09/18/2012 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 WEIMING XU and LAURA G. CORRAL __________ Appeal 2011-012442 Application 11/289,723 Technology Center 1600 __________ Before TONI R. SCHEINER, DONALD E. ADAMS, and JEFFREY N. FREDMAN, Administrative Patent Judges. FREDMAN, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to a method for managing an immunodeficiency disorder. The Examiner rejected the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We reverse. Appeal 2011-012442 Application 11/289,723 2 Statement of the Case Background “This invention relates to methods of treating, preventing and/or managing immunodeficiency disorders by the administration of one or more immunomodulatory compounds alone or in combination with other therapeutics” (Spec. 1, ll. 3-5). The Claims Claims 1, 3, 4, 17, 18, 21, 22, 31, and 32 are on appeal 1 . The sole independent claim, claim 1, is representative and reads as follows: 1. A method of treating or managing an immunodeficiency disease or disorder, which comprises administering to a patient in need of such treatment or management a therapeutically effective amount of an immunomodulatory compound, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein the immunodeficiency disease or disorder is adenosine deaminase deficiency, antibody deficiency with normal or elevated Igs, ataxia-tenlangiectasia, bare lymphocyte syndrome, common variable immunodeficiency, Ig deficiency with hyper-IgM, Ig heavy chain deletions, IgA deficiency, immunodeficiency with thymoma, reticular dysgenesis, Nezelof syndrome, selective IgG subclass deficiency, transient hypogammaglobulinemia of infancy, Wistcott-Aldrich syndrome, X-linked agammaglobulinemia, or X-linked severe combined immunodeficiency. 1 The claims were restricted and Appellants elected the disorder, IgA deficiency, and the compound 4-(amino)-2-(2,6-dioxo(3- piperidyl))- isoindoline-1,3-dione (also known as “actimid”). Appeal 2011-012442 Application 11/289,723 3 The issue The Examiner rejected claims 1, 3, 4, 17, 18, 21, 22, 31, and 32 under 35 U.S.C. § 103(a) as obvious over Robarge, 2 Punnonen, 3 Smith, 4 and Siwinska-Golebiowska 5 (Ans. 4-8). The Examiner finds that the “rejection is drawn to the embodiment of treating or managing a patient within the subpopulation having both DiGeorge syndrome and IgA deficiency or a patient having each of DiGeorge syndrome, IgA deficiency, and IgE deficiency” (Ans. 5). The Examiner finds that Robarge teaches “isoindole-imide compounds that are potent inhibitors of the production of TNF-α in mammals, the compounds are useful for treating or preventing diseases or disorders in mammals (abstract); the compounds include the elected compound actimid” (Ans. 5). The Examiner finds that Robarge teaches that “low T-cells are prominent in a number of immune deficiency syndromes including HIV infection and DiGeorge Syndrome” (Ans. 5). 2 Robarge et al., US 2003/0096841 A1, published May 22, 2003. 3 Punnonen et al., Soluble and Membrane-bound Forms of Signaling Lymphocytic Activation Molecule (SLAM) Induce Proliferation and Ig Synthesis by Activated Human B Lymphocytes, 185 J. EXPERIMENTAL MEDICINE 993-1004 (1997). 4 Smith et al., Increased Prevalence of Immunoglobulin A Deficiency in Patients with the Chromosome 22q 11.2 Deletion Syndrome (DiGeorge Syndrome/Velocardiofacial Syndrome), 5 CLINICAL DIAGNOSTIC LABORATORY IMMUNOLOGY 415-417 (1998). 5 Siwinska-Golebiowska et al., Immunological confirmation of allergy in children with hypoimmunoglobulinemia, 7 MD. WIEKU ROZWOJ. 279-87 (2003). Appeal 2011-012442 Application 11/289,723 4 The Examiner finds that “Punnonen teaches the CD40 ligand (CD40L) on activated CD4+ T cells, which interacts with CD40 on B cells, was shown to be a potent membrane-bound costimulatory molecule for proliferation and differentiation of both human and murine B cells” (Ans. 6- 7). The Examiner finds that “Smith teaches the prevalence of immunoglobulin A (IgA) deficiency in patients with DiGeorge Syndrome is 13%” (Ans. 7). The Examiner finds that “Siwinska-Golebiowska establishes that low IgE levels also accompany DiGeorge Syndrome” (Ans. 7). The Examiner finds that since “actimid modulates the production of TNF- and IL-1 and stimulates the production of IL-10 and the production of T-cells . . . and low T-cells are prominent in a number of immune deficiency syndromes including DiGeorge Syndrome, the administration of actimid for treating DiGeorge Syndrome would have been obvious” (Ans. 7). The Examiner finds “treating a patient in the subpopulation with both DeGeorge [sic] Syndrome and IgA deficiency . . . would have been obvious, based on the recognition that there is an overlap in the two patient populations” (Ans. 8). Appellants contend that “Robarge does not teach treating the recited diseases/conditions of claim 1, including the elected IgA deficiency or the combination of the elected compound with anti-CD40 antibody or CD40L” (App. Br. 13). Appellants contend that the ordinary artisan “would not have had a reasonable expectation that the administration of the compounds recited by the claims on appeal would be efficacious for the treatment of IgA deficiency.” (App. Br. 14). Appeal 2011-012442 Application 11/289,723 5 Appellants contend that “Robarge is clearly silent regarding whether the DiGeorge Syndrome patients as contemplated therein would or would not have IgA deficiency. As such, Applicants respectfully point out that Robarge, even in view of Smith's disclosure, cannot provide a proper basis to render the claimed methods obvious” (App. Br. 15). Appellants contend that the Examiner’s reasoning is “logically flawed because, under this logic, no new method of treatment claims would be allowable because prior disclosure of treatment of another disease would always render such claims obvious” (App. Br. 16). The issue with respect to this rejection is: Does the evidence of record support the Examiner’s conclusion that Robarge, Punnonen, Smith, and Siwinska-Golebiowska render claim 1 obvious? Findings of Fact The following findings of fact (“FF”) are supported by a preponderance of the evidence of record. 1. Robarge teaches “isoindole-imide compounds that have one or more of the following activities: modulation of the production of TNF; modulation of the production of IL-l; stimulation of the production of IL- 10, or stimulation of the production T-cells” (Robarge 1 ¶ 0003). 2. Robarge teaches that “abnormally low T-cell levels are prominent in a number of other immune deficiency syndromes, including DiGeorge Syndrome” (Robarge 1 ¶ 0010). 3. Punnonen teaches that “the role of CD40L appears to be crucial, as is clearly demonstrated in patients with hyper-IgM syndrome, Appeal 2011-012442 Application 11/289,723 6 who are unable to produce IgG, IgA, or IgE because of mutations in their genes encoding CD40L” (Punnonen 994, col. 1). 4. Smith teaches that a “total of 32 patients with the chromosome 22q11.2 deletion were examined for IgA deficiency. We report a 13% (n = 4) prevalence of IgA deficiency in patients with this syndrome” (Smith, abstract). 5. Siwinska-Golebiowska studied a group of “12 children who had combined immunodeficiency with hypoimmunoglobulinemia (3-AT; 8- Nijmegen S: 1 –Di George” (Siwinska-Golebiowska, abstract). Principles of Law “In rejecting claims under 35 U.S.C. § 103, the examiner bears the initial burden of presenting a prima facie case of obviousness. Only if that burden is met, does the burden of coming forward with evidence or argument shift to the applicant.” In re Rijckaert, 9 F.3d 1531, 1532 (Fed. Cir. 1993). “[R]ejections on obviousness grounds cannot be sustained by mere conclusory statements; instead, there must be some articulated reasoning with some rational underpinning to support the legal conclusion of obviousness.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007). “Inherency ... may not be established by probabilities or possibilities. The mere fact that a certain thing may result from a given set of circumstances is not sufficient.” MEHL/Biophile Int’l. Corp. v. Milgraum, 192 F.3d 1362, 1365 (Fed. Cir. 1999). Appeal 2011-012442 Application 11/289,723 7 Analysis We limit our consideration of the merits of the appealed rejections to the elected species. See Ex parte Ohsaka, 2 USPQ2d 1460, 1461 (Bd. Pat. App. Int. 1987). Thus, we read claim 1 as limited to the use of the elected actimid compound as the immunomodulatory compound and as limited to treatment of the elected IgA deficiency as the immunodeficiency disease (see App. Br. 7) . While Robarge generically teaches a large number of isoindole-imide compounds with activities including stimulation of the production of T-cells (FF 1), and Robarge teaches that low T-cell levels are associated with diseases including DiGeorge syndrome (FF 2), Robarge never specifically identifies actimid as a functional treatment for DiGeorge syndrome, nor does Robarge ever teach that actimid will have any effect on IgA deficiency. Punnonen and Siwinska-Golebiowska provide no evidence which supports a finding that actimid will have any impact on IgA deficiency or DiGeorge syndrome (FF 3, 5). Smith teaches that 13% of the 32 DiGeorge syndrome patients examined also had IgA deficiency (FF 4). Smith does not teach any treatment modalities, but does recognize that DiGeorge syndrome patients may have comorbidity with IgA deficiency (FF 4). We agree with Appellants that there would not have been a reasonable expectation of success in treating IgA deficiency with the actimid compound of Robarge. In Kubin, the court made clear that “where a defendant merely throws metaphorical darts at a board filled with combinatorial prior art possibilities, courts should not succumb to hindsight claims of obviousness.” Appeal 2011-012442 Application 11/289,723 8 In re Kubin, 561 F.3d 1351, 1359 (Fed. Cir. 2009). The obviousness rejection of these claims is such a situation, where the prior art gives an immense number of diseases which may be treated from cancer to heart failure to viral diseases (see Robarge 1 ¶¶ 0003-0010). In addition, the prior art also lists a very large genus of isoindole-imide compounds of an extensive Formula I, without any specific identification of actimid as particularly desirable for treatment of IgA deficiency (see Robarge 3-4 ¶¶ 0019-0041). Unlike Kubin, where performing the detailed methodology of cloning would necessarily result in obtaining a molecule within the genus of nucleic acids being claimed, there is no predictable expectation that selection of a particular disease condition and a particular molecule from Robarge would predictably, or even likely, result in treatment of the disease condition. There is even less likelihood that selection and treatment of DiGeorge syndrome with a particular compound, even with the Smith’s known association between DiGeorge syndrome and IgA deficiency, would necessarily and inherently result in successful treatment of IgA deficiency. The Examiner has not established, and we do not find, that the ordinary artisan would have reasonably and predictably selected actimid, would have reasonably and predictably chosen to use actimid to treat DiGeorge syndrome, and then would have reasonably predictably expected that this treatment would also treat the comorbidity of IgA deficiency along with DiGeorge syndrome. Appeal 2011-012442 Application 11/289,723 9 Conclusion of Law The evidence of record does not support the Examiner’s conclusion that Robarge, Punnonen, Smith, and Siwinska-Golebiowska render claim 1 obvious. SUMMARY In summary, we reverse the rejection of claims 1, 3, 4, 17, 18, 21, 22, 31, and 32 under 35 U.S.C. § 103(a) as obvious over Robarge, Punnonen, Smith, and Siwinska-Golebiowska. REVERSED alw