Ex Parte Kirk

Board of Patent Appeals and Interferences

Jan 12, 2009

10685003 (B.P.A.I. Jan. 12, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte IAN KIRK
__________

Appeal 2008-5579
Application 10/685,003
Technology Center 1600
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Decided: January 12, 2009
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Before TONI R. SCHEINER, ERIC GRIMES, and LORA M. GREEN,
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 final rejection of claims 3, 7-9, and 11. We have jurisdiction
under 35 U.S.C. § 6(b).
Appeal 2008-5579
Application 10/685,003

STATEMENT OF THE CASE
The claims are directed to a method of treating inflammation using
melagatran (COOH-CH2-(R)Cgl-Aze-Pab-H; Spec. 2: 10-11) or a derivative
thereof. Claim 3 is representative of the claims on appeal, and reads as
follows:
3. A method of treatment of inflammation which comprises
administering a therapeutically effective amount of melagatran, or a
pharmaceutically acceptable derivative, said derivative having the inhibitory
activity against thrombin or being a prodrug of melagatran, to a patient in
need of such treatment, wherein the prodrug is of the formula
R1O2C-CH2-(R)Cgl-Aze-Pab-OH
wherein R1 represents linear or branched C1-6 alkyl and the OH group
replaces one of the amidino hydrogens in Pab.

The Examiner relies on the following reference:
Antonsson WO 97/23499 Jul. 3, 1997

We affirm.

ISSUE
The Examiner concludes that claims 3, 7-9, and 11 are obvious over
Antonsson.
Appellant contends that the ordinary artisan would not have been
motivated by Antonsson to employ melagatran or one of the prodrugs of
melagatran recited in the claims in the treatment of inflammation.
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Thus, the issue on Appeal is: Would the ordinary artisan have been
motivated by Antonsson to employ melagatran or one of the prodrugs of
melagatran recited in the claims in the treatment of inflammation?

FINDINGS OF FACT
FF1 The Specification teaches that “melagatran elicits a notable
antiinflammatory effect . . . and may thus be used to treat inflammation in
preferably mammalian, and especially human, patients.” (Spec. 2.)
FF2 According to the Specification:
[M]elagatran, and derivatives and prodrugs thereof, are
preferably used in the treatment of inflammation in patients
with, or at risk of, a disease in which inhibition of thrombin is
desired or required (see, for example, those listed in
international patent application WO 97/23499), such as a
thrombotic disease. Although the treatment may be of patients
whose inflammatory and thrombotic diseases are unrelated, we
prefer that the treatment is of a patient with a thrombotic
disease in which inflammation plays a part in triggering
coagulation. For example, inflammation may arise in blood
vessel walls due to the presence and/or the action of microbes
and/or the agents released thereby, physical damage,
atheroscelorotic lesions and other inflammation-inducing
agents. It is preferred that melagatran, and derivatives and
prodrugs thereof, are used in the treatment of inflammation in
patients having, or at risk of having, a thrombus.

(Id. at 3-4.)
FF3 The Examiner rejects claims 3, 7-9, and 11 under 35 U.S.C. § 103(a)
as being obvious over Antonsson (Ans. 4). As Appellant does not argue
claims 7-9 and 11 separately, those claims stand or fall with claim 3. 37
C.F.R. § 41.37(c)(1)(vii).
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FF4 Antonsson is cited for teaching the use of the compounds of the
formula R1O(O)C-CH2-(R)Cgl-Aze-Pab-R2 as thrombin inhibitors (Ans. 4).
FF5 The Examiner finds further that Antonsson teaches that the
compounds may be used in the treatment of inflammatory conditions such as
edema (id.), and pancreatitis, which involves the inhibition of trypsin (id. at
4-5).
FF6 The Examiner acknowledges that Antonsson does not specifically
provide an example of using a specific melagatran compound in the
treatment of inflammation, but notes that the reference teaches “that
thrombin is known to activate a large number of cells such as neutrophils,
fibroblasts, endothelial cells and smooth muscle cells, and that the
melagatran compounds (as thrombin inhibitors) are useful for therapeutic
treatment of diseases related to activation of these cells such as an
inflammatory condition including edema.” (Id. at 4.)
FF7 The Examiner also finds that Antonsson teaches preferred compounds
in which R1 is methyl, ethyl, or propyl, and R2 is OH (id.).
FF8 The Examiner concludes:
At the time [the] invention was made, it would have been
obvious to one of ordinary skill that the preferred melagatran
compounds with formula (I) having methyl, ethyl or propyl as
R1, and OH as R2 are useful in treating an inflammatory
condition because Antonsson et al. indicate that inflammation
and other listed diseases would occur when cells such as
neutrophils, fibroblasts, endothelial cells and smooth muscle
cells are activated by thrombin, and melagatran compounds that
inhibit thrombin can be used to treat an inflammatory condition
(page 20, lines 9-21), which results in the claimed invention
and was, as a whole, prima facie obvious at the time the
claimed invention was made.
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(Id. at 5.)
FF9 Antonsson teaches that the compounds are “expected to have utility in
prophylaxis of re-occlusion (ie thrombosis) after thrombolysis, percutaneous
trans-luminal angioplasty (PTA) and coronary bypass operations; the
prevention of re-thrombosis after microsurgery and vascular surgery in
general.” (Antonsson 19.)
FF10 Antonsson teaches further that:
In addition to its effects on the coagulation process, thrombin is
known to activate a large number of cells (such as neutrophils,
fibroblasts, endothelial cells and smooth muscle cells).
Therefore, the compounds of the invention may also be useful
for the therapeutic and/or prophylactic treatment of idiopathic
and adult respiratory distress syndrome, pulmonary fibrosis
following treatment with radiation or chemotherapy, septic
shock, septicemia, inflammatory responses, which include, but
are not limited to, edema, acute or chronic atherosclerosis such
as coronary arterial disease, cerebral arterial disease, peripheral
arterial disease, reperfusion damage, and restenosis after
percutaneous trans-luminal angioplasty (PTA).

(Id. at 20.)
FF11 Thus, Antonsson teaches that the disclosed prodrugs of melagatran
may be used in PTA, both because of their effect on thrombin and as anti-
inflammatories.
FF12 Antonsson also teaches that “[c]ompounds of the invention that inhibit
trypsin and/or thrombin may also be useful in the treatment of pancreatitis.”
(Id. at 20.)

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PRINCIPLES OF LAW
The question of obviousness is resolved on the basis of underlying
factual determinations including: (1) the scope and content of the prior art;
(2) the level of ordinary skill in the art; (3) the differences between the
claimed invention and the prior art; and (4) secondary considerations of
nonobviousness, if any. Graham v. John Deere Co., 383 U.S. 1, 17 (1966).
The Supreme Court has recently emphasized that “the [obviousness] analysis
need not seek out precise teachings directed to the specific subject matter of
the challenged claim, for a court can take account of the inferences and
creative steps that a person of ordinary skill in the art would employ.” KSR
Int’l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007).

ANALYSIS
Appellant argues that the focus of Antonsson is prodrugs that are low
molecular weight thrombin inhibitors; thus, the ordinary artisan would not
have been motivated by Antonsson “to employ melagatran per se (which is
not even disclosed in Antonsson), and/or a very small number of specific
prodrugs of melagatran, for use in the treatment of inflammation, as
presently claimed.” (App. Br. 10.) Appellant asserts further that in
Antonsson “‘inflammatory responses’ is merely listed as another potential
disease that could be treated amongst a list of several other diseases.” (Id. at
10-11.) Appellant argues moreover that Antonsson only tests the thrombin
inhibiting ability of the disclosed compounds (id. at 11). According to
Appellant, “there is no evidence presented in Antonsson of any kind of link
between thrombin inhibitors and inflammation,” therefore “a person of
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ordinary skill would not have been led to believe that the anticoagulant
compounds disclosed by Antonsson would also be useful in treating
inflammation.” (Id.)
Appellant’s arguments are not convincing. First the fact that
Antonsson does not disclose the use of melagatran per se is irrelevant, as the
claims are not limited to the use of melagatran, but encompass the use of
prodrugs as taught by Antonsson. In addition, as to Appellant’s arguments
that the ordinary artisan would not have been motivated to use one of a small
number of specific prodrugs, the Examiner finds that Antonsson teaches that
preferred compounds are ones in which R1 is methyl, ethyl, or propyl, and
R2 is OH (FF7) (a finding that Appellant does not challenge), and thus
Antonsson does specifically point to the claimed prodrugs.
In addition, Antonsson teaches that the disclosed prodrugs have anti-
thrombolytic activity (FF4), and that thrombin is known to activate a large
number of cells (such as neutrophils, fibroblasts, endothelial cells and
smooth muscle cells) (FF10). Thus, Antonsson teaches, given that activity
of thrombin, that the prodrugs may be useful in the treatment of
inflammatory conditions such as edema (FF5 and FF10). Appellant has
provided no evidence that the ordinary artisan would doubt that activity,
given the ability of the compounds to act as anti-thrombolytics. Note that
arguments of counsel cannot take the place of evidence in the record. In re
Scarbrough, 500 F.2d 560, 566 (CCPA 1974).
Finally, the Specification teaches that the preferred treatment using
the claimed prodrugs is in the treatment of a thrombotic disease in which
inflammation plays a part (FF2). As taught by Antonsson, the disclosed
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prodrugs of melagatran may be used with percutaneous trans-luminal
angioplasty (PTA), where it would have activity as both an anti-thrombolytic
and an anti-inflammatory (FF9-11).

CONCLUSIONS OF LAW
We conclude that the ordinary artisan would have been motivated by
Antonsson to employ melagatran or the prodrugs of melagatran recited in the
claims in the treatment of inflammation. We thus affirm the rejection of
claims 3, 7-9, and 11 as being obvious over Antonsson.

TIME LIMITS
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

cdc

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