Ex Parte Xu et al

Patent Trial and Appeal Board

Sep 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”).
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Application 11/289,723

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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).
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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).
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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,
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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).

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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.”
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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.

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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
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