Ex Parte Knapp

Board of Patent Appeals and Interferences

Feb 28, 2006

09935442 (B.P.A.I. Feb. 28, 2006)

1
The opinion in support of the decision being entered today was not written
for publication and is not binding precedent of the Board.

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte DAVID KNAPP
__________

Appeal No. 2005-2690
Application No. 09/935,442
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ON BRIEF
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Before ADAMS, MILLS and GRIMES, Administrative Patent Judges.

MILLS, 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 1-6, 8-13, 15, 26-28, and 47-52, which are all the claims currently
pending in this application. Claim 1 is illustrative of the claims on appeal and reads as
follows:
1. A vascular medical device comprising

fibrinogen as a precursor compound and thrombin as an activator
compound,

wherein said medical device is adapted, upon placement at an
administration site within a patient, to separately release said precursor
compound and said activator compound such that said activator compound

2
interacts with said precursor compound in vivo and converts said precursor
compound into activated form for local delivery,

and wherein said vascular medical device is selected from a
vascular catheter, a vascular stent and a vascular graft.

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Background
The specification discloses “a therapeutic medical article…which comprises a
medical article, a precursor compound and an activator compound. The medical article
is adapted, upon administration to a patient, to release the precursor compound and
the activator compound such that the activator compound interacts with the precursor
compound and converts the precursor compound into activated form for local delivery.”
Page 1-2, paragraph [0006]. One particular advantage is that these compounds “can
be generated in the body at the site of interest, rather than elsewhere in the body
where the therapeutic agents have little therapeutic effect or even a harmful effect.”
Page 3, paragraph [0012]. Specifically, the precursor compound reacts with the
activator compound, which can “lead to therapeutic outcomes, including restenosis1
prevention.” Page 10-11, paragraph [0039]. In a preferred embodiment, the
specification also states “precursor/activator compounds that can be
used…are…fibrinogen and thrombin.” Page 2, paragraph [0007]. Also, “[p]referred
medical articles include vascular medical devices (e.g., injection catheters, infusion
balloon catheters, coated balloon catheters, coated stents and coated stent-grafts).”
Page 2, paragraph [0008]. In addition, precursor and activator molecules can also be
released separately and in vivo. Page 6, paragraphs [0024]-[0026]; page 11,
paragraph [0042].

1 According to Dinh (U.S. Patent No. 5,510,077, of record), restenosis is the reclosure of a peripheral or
coronary artery following trauma to that artery, such as, for example, by balloon dilation, ablation,
atherectomy, or laser treatment of the artery. Column 1, lines 13-17. Restenosis is believed to be a natural
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healing reaction to injury…the healing reaction begins with the thrombotic mechanism at the site of injury.
Column 1, lines 20-24. “Fibrin is said to be highly nonthrombogenic and tissue compatible and promotes
uniform propagation of cells that regenerate the intima.” Column 2, lines 10-13.
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DISCUSSION
Obviousness
The examiner rejected claims 1-6, 8-13, 15, 26-28, and 47-52 under 35 U.S.C.
§ 103(a) as obvious over Dinh2 in view of Delmotte3 and Sawhney.4
In rejecting claims under 35 U.S.C. § 103, the examiner bears the initial burden of
presenting a prima facie case of obviousness. See In re Rijckaert, 9 F.3d 1531, 1532,
28 USPQ2d 1955, 1956 (Fed. Cir. 1993). A prima facie case of obviousness is
established when the teachings from the prior art itself would appear to have suggested
the claimed subject matter to a person of ordinary skill in the art. In re Bell, 991 F.2d
781, 783, 26 USPQ2d 1529, 1531 (Fed. Cir. 1993). Furthermore, it is well-established
that the conclusion that the claimed subject matter is prima facie obvious must be
supported by evidence, as shown by some objective teaching in the prior art or by
knowledge generally available to one of ordinary skill in the art that would have led that
individual to combine the relevant teachings of the references to arrive at the claimed
invention. See In re Fine, 837 F.2d 1071, 1074, 5 USPQ2d 1596, 1598 (Fed. Cir. 1988).
With this as background, we analyze the prior art applied by the examiner in the
rejection of the claims on appeal.
It is the examiner’s position that (Answer, pages 3-4):

2 Dinh et al., U.S. Patent No. 5,510,077, issued April 23, 1996.
3 Delmotte et al., U.S. Patent No. 5,989,215, issued November 23, 1999.
4 Sawhney et al., U.S. Patent No. 6,352,710, issued March 5, 2002.
The invention of Dinh is directed to the use of an intraluminal stent
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comprising fibrin for the treatment of restenosis and stent thrombosis.
According to the procedure of Dinh a stent is prepared by first polymerizing
fibrin in a molded cavity, in which the shape of the cavity defines the shape
of a fibrin stent. ....
Dinh does not teach the claimed activator and precursor in their
medical device. ....
Delmotte et al teaches a fibrin delivery device and a method of
forming fibrin on a wound surface to control bleeding and tissue sealing.
The device of Delmotte comprises a first and second biochemically reactive
liquid, comprising fibrinogen and thrombin respectively, in separate
containers. The two liquids are in communication with a spray unit, capable
of atomizing both liquids, when sprayed on the wound surface. Fibrinogen
and thrombin, upon spraying, forms fibrin glue (a barrier material) at the
surface of the wound (col. 3, lines 11-67). ... According to the invention of
Delmotte, the polymerization of fibrin occurs only at the site of
administration. ... Delmotte fails to suggest coating a stent.

We do not find that the examiner has provided sufficient evidence to support a
prima facie case of obviousness. We do not find the evidence would have provided one
of ordinary skill in the art with sufficient motivation to substitute a separately released
fibrinogen and thrombin for conversion to an activated fibrin form for local delivery, for
the fibrin coating in the vascular stent of Dinh. In particular, we do not find where the
examiner has indicated, or where the references disclose, that separately released
fibrinogen and thrombin for conversion to an activated fibrin form for local delivery, can
be incorporated into or adapted to a medical device, such as the vascular stent of Dinh.
As argued by appellant, Dinh teaches away from providing thrombin and
fibrinogen separately at the treatment site for in situ polymerization. Brief, page 6. Dinh
states that “[p]referably the coagulating effect of any residual coagulation protein in the
fibrin should be neutralized before employing it in the stent ... in order to prevent clotting
at the fibrin interface with blood after stent implantation.” Col. 5, lines 7-11.
In addition, appellant argues (Brief, page 7) that Delmotte
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warns of problems that may occur if fibrinogen and thrombin are separately
introduced for in situ polymerization from such a spray method. In this
connection Delmotte states that “the lower the amount of residual
fibrinogen, the better the non-adhesive properties of the fibrin film, since
fibrinogen in vivo may promote fibrin formation and thus adhesion
formation.” (Col. 7, lines 1-4)(emphasis added).

In view of the above, it would appear that Dinh suggests that it is critical that the
final fibrin product coating the stent must be in a form so as to avoid clotting at the fibrin
interface. Also understood from Delmotte, is that the acceptability for medical use of the
final fibrin form upon polymerization in situ is dependent upon the amount and form of
the fibrinogen and thrombin used. Added to these concerns, one of ordinary skill in the
art would have recognized at least some level of unpredictability associated with in situ
fibrin formation on a medical device, especially one implanted into the heart.
Furthermore, Delmotte describes the application of fibrin glues and films to
prevent adhesions associated particularly with surgical procedures in the abdominal
cavity. Column 1, lines 20-45. Delmotte does not suggest that the medical devices
adapted to deliver fibrin to treat abdominal adhesions address the same or similar
problems associated with the prevention of vascular restenosis.
In supplement to the above, while the examiner argues “Delmotte suggests
different types of fibrin glues can be prepared by altering the amount of thrombin used
and allowing formation of fibrin at the site of administration by separately providing
fibrinogen and thrombin” (Answer, page 5), Delmotte does not provide for “separate
release” of the precursor and activator compounds from an adapted medical device for
local delivery, as claimed. Instead, in the device of Delmotte, the precursor and activator
compounds begin in separate containers but are pressurized through a single spray unit,
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and thus the precursor and activator compounds are not “separately released” as
required by the claims. Column 8, lines 31-42. Appellant argues that, in Delmotte,
“mixing of fluids in each syringe occurs inside the connecting head.” Column 2, lines 49-
56.
Sawhney teaches coating medical devices with compositions that polymerize in
situ, preferably upon exposure to light. Sahwney, however, acknowledges additional
problems associated with use of fibrin glues coating medical devices, teaching they have
little flexibility or elasticity once their deposition is complete. Column 2, lines 29-31. “It is
believed that this lack of compliance (i.e., high elastic modulus and low elongation at
rupture) is an important reasons why seals formed with these and related prior-art
materials are likely to fail prematurely, especially when the area which is joined or sealed
is subject to deformation.” Column 2, lines 33-39.
The Examiner bears the burden of establishing a prima facie case of obviousness
based upon the prior art. The Examiner can satisfy this burden only by showing some
objective teaching in the prior art or that knowledge generally available to one of ordinary
skill in the art would lead that individual to combine the relevant teachings of the
references. In re Fritch, 972 F.2d 1260, 1265, 23 USPQ2d 1780, 1783 (Fed. Cir. 1992).
An adequate showing of motivation to combine requires “evidence that ‘a skilled artisan,
confronted with the same problems as the inventor and with no knowledge of the claimed
invention, would select the elements from the cited prior art references for combination in
the manner claimed.’” Ecolochem, Inc. v. Southern Calif. Edison Co., 227 F.3d 1361,
1375, 56 USPQ2d 1065, 1076 (Fed. Cir. 2000).
In view of the above, we do not find the examiner has provided sufficient evidence
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that one of ordinary skill in the art confronted with the same problems as the inventor, i.e.
prevention of restenosis upon stent implantation, and with no knowledge of the claimed
invention, would select the elements from the cited prior art references for combination in
the manner claimed, to support a prima facie case of obviousness. We do not find that
the evidence before us provides such motivation or evidences that one of ordinary skill in
the art would have expected that the incorporation of a separately released fibrinogen
and thrombin for conversion to an activated fibrin form for local delivery into an adapted
medical device which is a vascular catheter, a vascular stent or a vascular graft, would
have addressed clotting problems associated with the fibrin formation upon stent
implantation and would have addressed issues associated with restenosis upon stent
implantation. The rejection of claims 1-6, 8-13, 15, 26-28, and 47-52 over Dinh in view
of Delmotte and Sawhney is reversed.

CONCLUSION
The rejection of claims 1-6, 8-13, 15, 26-28, and 47-52 under 35 U.S.C. § 103 for
obviousness over Dinh in view of Delmotte and Sawhney is reversed.
No time period for taking any subsequent action in connection with this appeal
may be extended under 37 CFR § 1.136(a).

REVERSED

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Application No. 09/935,442

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Donald E. Adams )
Administrative Patent Judge )
)
)
) BOARD OF PATENT
Demetra J. Mills )
Administrative Patent Judge ) APPEALS AND
)
) INTERFERENCES
)
Eric Grimes )
Administrative Patent Judge )

Appeal No. 2005-2690
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