Ex Parte Schrader

Board of Patent Appeals and Interferences

Jun 8, 2010

10311760 (B.P.A.I. Jun. 8, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte HARALD SCHRADER
__________

Appeal 2009-012177
Application 10/311,760
Technology Center 1600
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Decided: June 8, 2010
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Before DEMETRA J. MILLS, LORA M. GREEN, and
FRANCISCO C. PRATS, Administrative Patent Judges.

GREEN, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. § 134 from the
Examiner’s rejection of claims 16, 18 and 21-29. We have jurisdiction
under 35 U.S.C. § 6(b).

Appeal 2009-012177
Application 10/311,760

STATEMENT OF THE CASE
Claim 16 is representative of the claims on appeal, and read as
follows:
16. A method for the treatment of a vascular headache condition not
caused by hypertension, comprising administering to a patient in
need of such treatment a therapeutically effective amount of an
angiotensin II type 1 receptor antagonist selected from the group
consisting of candesartan and candesartan cilexetil.

The following grounds of rejection are before us for review:
Claims 16, 18, and 21-29 stand rejected under 35 U.S.C. § 103(a) as
being rendered obvious by the combination of Chakravarty,1 Hansson,2
Naka ’444,3 Naka ’110,4 Doctor’s Guide,5 and Nishimura.6
We reverse.

ISSUE
When the evidence of obviousness is weighed with Appellant’s
rebuttal evidence, does the preponderance of evidence of record support the
Examiner’s conclusion of obviousness?

1 Chakravarty, EP 0 510 813 A1, issued March 24, 1992.
2 Hansson et al., Headache in Mild-to-Moderate Hypertension and Its
Reduction by Irbesartan Therapy, 160 ARCH INTERN MED. 1654-1658
(2000).
3 Naka, US 5,196,444, issued Mar. 23, 1993.
4 Naka, US 5,703,110, issued Dec. 30, 1997.
5 Doctor’s Guide, http://www.pslgroup.com/dg/394BA.htm. (1997).
6 Nishimura et al., The angiotensin AT1 receptor antagonist CV-11974
regulates cerebral blood flow and brain angiotensin AT1 receptor
expression, 93 BASIC RES CARDIOL 63-68 (1998).
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FINDINGS OF FACT
FF1 The Specification teaches that the “present invention relates to the use
of an angiotensin II (AT II) type 1 receptor antagonist in the manufacture of
a medicament for the prophylactic and/or therapeutic treatment of vascular
headaches, and in particular as a medicament for the treatment of migraine.”
(Spec. 1.)
FF2 As taught by the Specification, the invention uses angiotensin II type I
receptor antagonists of the general formula I, wherein A is selected from
specified groups:

(Id. at 4-7.) The Specification teaches that such compounds include losartin,
candesartan cilexetil, irbesartan, and candesartan. (Id. at 7.) The
Specification teaches that the preferred compounds are candesartan cilexetil
and candesartan. (Id.)
FF3 According to the Specification:
In the present invention, the term “vascular headache
condition” is intended to include any kind of vascular
headaches, in particular migraine, cluster headache, post-
traumatic headache, tension headache, muscular headache and
headache caused by one or more vascular diseases. The present
invention is preferably used for treating subjects suffering from
or susceptible to, migraine. A further aspect of the invention, is
a vascular headache condition not due to hypertension (i.e. not
caused by hypertension).
(Id. at 8.)
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FF4 We adopt the Examiner’s fact findings in the statement of the
rejection as our own. (Ans. 3-5.) We also make the additional findings of
fact.
FF5 Chakravarty teaches compounds of the formula:

(Chakravarty, 3.) Chakravarty teaches that the compounds are “angiotensin
II antagonists and are useful in the treatment of hypertension and congestive
heart failure.” (Id. at 2.)
FF6 Chakravarty teaches further that the compounds
may also be expected to be useful in the treatment of secondary
hyperaldosteronism, primary and secondary pulmonary
hyperaldosteronism, primary and secondary pulmonary
hypertension, renal failure such as diabetic nephropathy,
glomerulonephritis, scleroderma, glomerular sclerosis,
proteinuria of primary renal disease, end stage renal disease,
renal transplant therapy, and the like, renal vascular
hypertension, left ventricular dysfunction, diabetic retinapathy
and in the management of vascular disorders such as migraine,
Raynaud's disease, luminal hyperclasia, and to minimize the
atherosclerotic process.

(Id. at 39 (emphasis added).)
FF7 Naka ’110 teaches compounds of formula I
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(Naka ’110, col. 2, ll. 40-48.)
FF8 Naka ’110 teaches that the compounds “having potent
antihypertensive activity and strong angiotensin II antagonistic activity,
which are useful as therapeutic agents for treating circulatory diseases such
as hypertensive diseases, heart diseases . . ., strokes, cerebral apoplexy,
nephritis, etc.” (Id. at col. 1, ll. 17-22.)
FF9 Culman7 teaches two types of angiotensin II receptor subtypes have
been identified, AT1 and AT2. (Culman, Abstract.)
FF10 Culman teaches that “[s]everal selective and high affinity AT1
receptor antagonists are currently available, including candesartan,
eprosartan, irbesartan, losartan, telmisartan and valsartan.” (Id. at S66, first
column.)
FF11 Culman teaches that in vitro binding studies show that “candesartan
has a remarkable high affinity for the AT1 receptor, compared with other
antagonists.” (Id.) Culman teaches further that candesartan dissociates
extremely slowly from the receptor, which seems to provide
“insurmountable inhibition since insurmountable antagonism is
characteri[z]ed by a long-lasting inhibition of the receptor by the
antagonist.” (Id.)

7 Culman et al., The rennin-angiotensin system in the brain: possible
therapeutic implications for AT1-receptor blockers, 16 J. HUMAN
HYPERTENSION S64-S70 (2002).
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FF12 Culman teaches that irbesartan appears to be able to cross the blood-
brain barrier more effectively than losartan, and that telmisartan can also
penetrate the brain barrier. (Id. at S66, paragraph bridging the columns.)
FF13 Culman teaches, however, that in their studies:
[C]andesartan produced the most effective inhibition of brain
AT1 receptors. Candesartan produced a complete 24-h,
blockade of centrally mediated angiotensin II effects at doses 5-
10 times lower than the losartan or irbesartan doses required to
inhibit central angiotensin II activity. Chronic systemic
treatment with candesartan also dose-dependently decreased
AT1 binding in brain areas locali[z]ed outside, as well as inside,
the blood-brain barrier. The effective and long-lasting blockade
of brain AT1 receptors displayed by candesartan may be
attributed to the insurmountable antagonism, characteri[z]ed by
tight binding and slow dissociation from the receptor. This
suggests that systematically administered candesartan may
exhibit a long duration of action in the brain.

(Id. as S66, second column.)

PRINCIPLES OF LAW
One way for a patent applicant to rebut a prima facie case of
obviousness is to make a showing of “unexpected results,” i.e.,
to show that the claimed invention exhibits some superior
property or advantage that a person of ordinary skill in the
relevant art would have found surprising or unexpected. The
basic principle behind this rule is straightforward-that which
would have been surprising to a person of ordinary skill in a
particular art would not have been obvious.

In re Soni, 54 F.3d 746, 750 (Fed. Cir. 1995).
“When prima facie obviousness is established and evidence is
submitted in rebuttal, the decision-maker must start over.” In re Rinehart,
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Application 10/311,760

531 F.2d 1048, 1052 (CCPA 1976); In re Hedges, 783 F.2d 1038, 1039
(Fed. Cir. 1986) (“If a prima facie case is made in the first instance, and if
the applicant comes forward with reasonable rebuttal, whether buttressed by
experiment, prior art references, or argument, the entire merits of the matter
are to be reweighed”).
In addition, “when unexpected results are used as evidence of
nonobviousness, the results must be shown to be unexpected compared with
the closest prior art.” In re Baxter Travenol Labs., 952 F.2d 388, 392 (Fed.
Cir. 1991). A showing of unexpected results must also be commensurate in
scope with the breadth of the claims. In re Grasselli, 713 F.2d 731, 743
(Fed. Cir. 1983).

ANALYSIS
Appellant argues that Culman provides evidence of unexpected
results. (App. Br. 9.) Culman, Appellant asserts, teaches that “‘candesartan
produced the most effective inhibition of brain AT1 receptors.’” (Id. at 10
(quoting Culman, S66).) According to Appellant,
when considered in view of the Doctor’s Guide, the reported
penetration of the blood-brain barrier and superior blockade of
brain ATI receptors displayed by candesartan relative to other
AT1 receptors antagonists suggests a patentable improvement
over prior art methods of treating migraine. This advantage is
both superior and unexpected in view of the cited prior art.

(App. Br. 10.)
The Examiner finds that Culman is not evidence of unexpected results
as Nishimura demonstrates that “candesartan is known of being able to cross
[the] blood-brain barrier at the time the claimed invention was made.” (Ans.
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Application 10/311,760

5.) The Examiner further notes that Culman compares candesartan to
irbesartan, losartan, and telmisartan, and that those compounds are
structurally different from those disclosed by Chakravarty, and thus Culman
does not compare candesartan to the closest prior art. (Id. at 7.) Finally,
according to the Examiner, the evidence is not commensurate in scope with
the claimed invention, as the claims are directed to treating migraine,
whereas the evidence shows binding to the AT1 receptor. (Id.)
Appellant responds that Culman provides a comparison to the closest
prior art. (App. Br. 8.) According to Appellant, the Examiner acknowledges
in the statement of the rejection that Chakravarty does not teach the use of
the compounds in the claimed method, and relies on Hansson and the Naka
references to make up that deficiency. (Id.) Thus, Appellant asserts,
Chakravarty is not the closest prior art as asserted by the Examiner. (Id.)
We conclude that the Examiner has set forth a prima facie case of
obviousness. We conclude further, however, that when the evidence of
obviousness is weighed with Appellant’s rebuttal evidence, in the form of
Culman, the preponderance of the evidence supports the nonobviousness of
the claims. Specifically, Culman teaches that candesartan has the
unexpected property of producing the most effective inhibition of brain AT1
receptors. (See, e.g., FF13.)
We do not agree with the Examiner that the showing in Culman is not
commensurate in scope with the claims as the claims are directed to the
treatment of a vascular headache condition not caused by hypertension. The
Examiner relies on Chakravarty as demonstrating that angiotensin II
antagonists may be used to treat a variety of vascular disorders such as
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Application 10/311,760

migraine. (Ans. 3-4.) The Examiner relies on the Naka references and
Hansson for the specifically claimed angiotensin II antagonists. (Id. at 4.)
Thus, the rejection relies on the property of the claimed compounds as being
angiotensin II antagonists for the treatment of a vascular condition such as
migraine, and Culman teaches that candesartan has unexpected properties as
an angiotensin antagonist.
We also do not agree with the Examiner that Chakravarty is the
closest prior art. Chakravarty is drawn to angiotensin II antagonists that are
different in structure from the claimed compounds, whereas the Naka
references and Hansson teach compounds that encompass compounds as set
forth by Formula I of the instant Specification, such as losartin and
irbesartan. Thus, we agree with Appellant that Culman compares
candesartan to the closest prior art and teaches that candesartan has
unexpected properties as an angiotensin antagonist.
.

CONCLUSION OF LAW
When the evidence of obviousness is weighed with Appellant’s
rebuttal evidence, we conclude that the preponderance of evidence of record
does not support the Examiner’s conclusion of obviousness.
We thus reverse the rejection of claims 16, 18, and 21-29 under 35
U.S.C. § 103(a) as being rendered obvious by the combination of
Chakravarty, Hansson, Naka ’444, Naka ’110, Doctor’s Guide, and
Nishimura.

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Appeal 2009-012177
Application 10/311,760

REVERSED

cdc

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