Ex Parte DeLuca et al

Patent Trial and Appeal Board

Nov 1, 2012

11231049 (P.T.A.B. Nov. 1, 2012)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte HECTOR F. DELUCA, EHREN N. RUDOLPH,
LAURA MCCARY BLOSS, and JULIA B. ZELLA
__________

Appeal 2012-001735
Application 11/231,049
Technology Center 1600
__________

Before JEFFREY N. FREDMAN, ERICA A. FRANKLIN, and
SHERIDAN K. SNEDDEN, Administrative Patent Judges.

SNEDDEN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to methods
of delaying the onset of Type I diabetes. The Examiner has rejected the
claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm.

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Application 11/231,049

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STATEMENT OF THE CASE
According to Appellants, the invention relates to methods of delaying
the onset of diabetes by administering a vitamin D compound during a
detectable treatment window. (See e.g., Specification, 3.) Specifically, a
patient is treated “after the development of at least two autoantibodies
associated with diabetes, most notably selected from autoantibodies to
insulin, glutamic acid decarboxylase, or insulinoma-associated protein” and
“before the patient has developed a blood glucose level of 150 mg/dl.” (Id.)
Claims 1-6, 8-12 and 14-15 are on appeal. The claims have not been
argued separately and therefore stand or fall together. 37 C.F.R.
§ 41.37(c)(1)(vii). Claim 1 is representative and reads as follows
1. A method of delaying the onset of Type I diabetes or symptoms
thereof in a human patient, comprising:
detecting the presence of at least two autoantibodies indicative
of Type I diabetes in the patient, and,
orally administering to the patient a therapeutically effective
amount of a vitamin D compound, wherein the vitamin D compound
is administered to the patient before the patient's blood sugar level
increases to 150 mg/dl, the blood sugar level measured as an average
of 5 samples taken throughout a day at least 2 hours apart,
wherein the onset of Type I diabetes or diabetes symptoms
thereof is delayed.

The claims stand rejected as follows:
I. Claims 1-6, 8-12 and 14-15 under 35 U.S.C. 103(a) as being
unpatentable over the combination of Mathieu et al. (U.S. Patent
5,665,387, issued Sep. 9, 1997), Ziegler et al. (Autoantibody
Appearance and Risk for Development if Childhood Diabetes in
Offspring of Parents With Type 1 Diabetes, 48 DIABETES 460-468
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(1999)) and Khalil (Spectroscopic and Clinical Aspects of
Noninvasive Glucose Measurements, 45 CLINICAL CHEMISTRY 165-
177 (1999)).
I.
Issue
The Examiner concludes that the claimed subject matter is obvious
over the combined prior art. (See Ans. 7.)
Appellants contend that “the skilled artisan considering Mathieu,
Ziegler and Khalil at the time of the invention would not have a reasonable
likelihood of success in shifting the early treatment window taught by
Mathieu until after at least two autoantibodies are detected in the patient, as
required by the rejected claims.” (App. Br. 10.)
The issue is:
Does the evidence of record support the Examiner‟s conclusion that
the combination of Mathieu, Ziegler and Khalil render obvious the method
of claim 1?

Findings of Fact
FF1. The Examiner finds that
[s]ince Mathieu teaches the administration of 1α, 25-
dihydroxyvitamin D3 (1, 25(OH)2 D3) and it is known in the art
that autoantibodies to β-cell antigens precede the development
of type 1 diabetes and are commonly used as sensitive markers
to identify the preclinical period of diabetes type I with the fact
that autoimmune destruction of β-cells leads to Type I diabetes
as taught by Ziegler, one of ordinary skills would expect that in
testing an individual for the autoantibodies in order to begin the
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administration of 1α, 25-dihydroxyvitamin D3 (1, 25(OH)2 D3)
to inhibit the destruction of β-cells, which is known to cause
Type I diabetes.

(Ans. 8-9.)
FF2. Mathieu discloses as follows:
The invention thus relates to a method for treating
primary autoimmune diabetes by administering a suitable dose
of one or more vitamin D (analogue(s)) during a suitable period
of time to a subject who has a predisposition to develop
autoimmune diabetes. The vitamin D analogue(s) is/are
administered in an amount to modulate the immune system in
an animal or patient to which the amount is administered. A
large number of other analogues of 1α,25(OH)2D3 which
display a dissociation of their potency to induce cell
differentiation/immune effects and their calcemic effects in
vivo, have a variable degree of similar protective effects and
are able to induce primary or secondary prevention of type I
diabetes.

(Mathieu, col. 2, ll. 36-41; emphasis added.)
FF3. The Examiner finds that “Mathieu does not expressly teach the
detection of at least two autoantibodies or testing blood sugar levels an
average of 5 times daily.” (Ans. 6.)
FF4. The Examiner finds that “Ziegler teaches that autoantibodies to
β-cell antigens precede the development of type 1 diabetes and are
commonly used as sensitive markers to identify the preclinical period of
diabetes type I” and that that “[o]ne would have been motivated to detect at
least two autoantibodies” based on the teachings of Ziegler. (Id.)
FF5. Zeigler discloses the results of a study “to determine
autoantibody distributions and the chronology of antibody appearance from
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birth in offspring of parents with type 1 diabetes” and found that “[r]isk for
type 1 diabetes was highest in those with more than one islet autoantibody.”
(Zeigler, p. 465, left col.)
FF6. Zeigler discloses as follows:
In conclusion, our data demonstrate that autoimmunity in
children of parents with type 1 diabetes is initiated very early in
life, with a first peak of antibody appearance by the age of 2
years, that IAAs are present in the majority of these children in
the first sample with autoantibodies, and that the detection of
multiple antibodies at 2 years of age in offspring of parents
with type 1 diabetes is associated with a high risk of
progression to disease by age 5 years. These findings need to
be confirmed in studies from the general population, but with
this knowledge, new concepts of screening programs and
intervention strategies aiming to modulate the early stage of the
disease process may be considered.

(Zeigler, ¶ spanning pp. 467 and 468; emphasis added.)

Principles of Law
“Obviousness does not require absolute predictability of success ....
For obviousness under § 103, all that is required is a reasonable expectation
of success.” In re O’Farrell, 853 F.2d 894, 903-904 (Fed. Cir. 1988). A
critical step in analyzing these expectations is “casting the mind back to the
time of invention, to consider the thinking of one of ordinary skill in the art,
guided only by the prior art references and the then-accepted wisdom in the
field.” In re Kotzab, 217 F.3d 1365, 1369 (Fed. Cir. 2000).

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Analysis
Appellants contend that Mathieu does not inform a person of ordinary
skill in the art “„that 1α, 25(OH)2 D3 and analogs of 1α, 25(OH)2 D3 can
delay the onset of diabetes even after indicators of diabetes, such as insulitis
or the presence of autoantibodies to insulin, have been detected.‟” (App. Br.
8, quoting Declaration of Dr. DeLuca, submitted Nov. 18, 2009.) Appellants
further argue that “[a]lthough Ziegler indicates that the appearance of
autoantibodies correlates to a higher risk of contracting diabetes at a later
time, it does not speak to the predictability or success of shifting a diabetes
treatment regimen to a later time frame.” (App. Br. 8.)
We are not persuaded by Appellants‟ arguments. Rather, we agree
with the fact finding and analysis of the Examiner which we adopt as our
own. (Ans. 5-15.) In particular, we note that, for obviousness under § 103,
all that is required is a reasonable expectation of success. In re O’Farrell,
853 F.2d at 904. Here, Mathieu teaches the ability of vitamin D compounds
to induce primary or secondary prevention of Type I diabetes and that these
compounds may be administered to subjects who have a predisposition to
developing autoimmune diabetes. (FF2.) Zeigler teaches that the risk for
subjects having a predisposition to developing autoimmune diabetes is
highest in those with more than one islet autoantibody. (FF5 and FF6.)
Thus, we agree with the Examiner‟s conclusion that a person of ordinary
skill in the art would have had a reasonable expectation of success in treating
subjects identified as high risk using the techniques of Zeigler with vitamin
D compounds, which are taught by Mathieu to be useful in prevention of
autoimmune diabetes. (See e.g., FF1 and FF4.)
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While we acknowledge the expertise of Dr. Hector DeLuca, we find
that the Declaration does not carry significant persuasive weight. In re Am.
Acad. Of Sci. Tech Ctr., 367 F.3d 1359, 1368 (Fed. Cir. 2004) (“The Board
has broad discretion as to the weight to give to declarations offered in the
course of prosecution.”) In particular, we note that the Declaration fails to
consider what the combined teachings of the prior art would have taught a
skilled artisan regarding the predictability or success of delaying the onset of
Type 1 diabetes or symptoms in a human patient upon detection of the
presence of at least two autoantibodies indicative of Type 1 diabetes in the
patient. That is, Mathieu expressly teaches administering vitamin D analogs
to “a subject who has a predisposition to develop autoimmune diabetes”
(Mathieu, col. 2, ll. 36-41; FF 2) and Ziegler teaches that the “[r]isk for type
1 diabetes was highest in those with more than one islet autoantibody.”
(Zeigler, p. 465, left col.; FF 5). Therefore, contrary to the Declaration,
Ziegler establishes a predisposition for autoimmune diabetes when more
than one autoantibody is present in a patient (FF 5) and Mathieu teaches
administering vitamin D analogs to patients with a predisposition for
autoimmune diabetes, which together reasonably provide a reason and
expectation of success in treating Ziegler‟s at risk patients with Mathieus
vitamin D analogs.

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Conclusion of Law
The evidence of record supports the Examiner‟s conclusion that the
combination of Mathieu, Ziegler and Khalil renders obvious the method of
claim 1.

SUMMARY
We affirm the rejection of claim 1 under 35 U.S.C. 103(a) as being
unpatentable over the combination of Mathieu, Ziegler and Khalil. Pursuant
to 37 C.F.R. § 41.37(c)(1)(vii)(2006), we also affirm the rejection of claims
2-6, 8-12 and 14-15, as these claims were not argued separately.

AFFIRMED

cdc