Ex Parte Edelman et al

Patent Trial and Appeal Board

Jun 21, 2013

11440529 (P.T.A.B. Jun. 21, 2013)

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.
11/440,529 05/25/2006 Elazer Edelman 17648-0069 (MIT 11284) 7311
29052 7590 06/24/2013
SUTHERLAND ASBILL & BRENNAN LLP
999 PEACHTREE STREET, N.E.
Suite 2300
ATLANTA, GA 30309
EXAMINER
BLAND, LAYLA D
ART UNIT PAPER NUMBER
1623
MAIL DATE DELIVERY MODE
06/24/2013 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 ELAZER EDELMAN and MARK LOVICH1
__________

Appeal 2011-011021
Application 11/440,529
Technology Center 1600
__________

Before ERIC GRIMES, ERICA A. FRANKLIN, and
SHERIDAN K. SNEDDEN, Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a
therapeutic method, which have been rejected for obviousness. We have
jurisdiction under 35 U.S.C. § 6(b).
We reverse.

1 Appellants state that the Real Party in Interest is Massachusetts Institute of
Technology (Appeal Br. 2).
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STATEMENT OF THE CASE
During open-heart procedures, a “cardiopulmonary bypass (CPB)
circuit[ ] assumes the heart and lungs’ role of supplying oxygenated blood to
the rest of the body” (Spec. 1, ¶ 3). “Weaning a patient off cardiopulmonary
bypass (CPB) is a critical step of cardiac surgical procedures” (id. at 3, ¶ 7).
“Inotropic agents are one approach used to enhance a high-risk patient’s
ability to wean from CPB. Pharmacologic inotropic agents enhance
myocardial contractility,” and include norepinephrine and dopamine. (Id. at 4,
¶ 10.) “Each of these compounds, while increasing the inotropic state of the
heart, has limitations that restrict the doses that can be given intravenously”
(id.).
Claims 26-28, 35, 37, 38, and 40-47 are on appeal. Claim 26 is the
only independent claims and reads as follows:
26. A method of delivering a positive cardiac inotropic agent to the
heart of a human subject, comprising:
providing a delivery vehicle which is in the form of an adherent
patch which comprises at least one positive inotropic agent and a
barrier that is non-permeable to the positive inotropic agent, the
barrier being effective to allow release of the positive inotropic agent
toward the myocardium and to minimize release into the pericardial
fluid;
adhering the delivery vehicle onto an outer surface of the heart
away from the sinoatrial node of a subject in need of treatment; and
releasing a therapeutically effective amount of the positive
inotropic agent in a controlled manner from the delivery vehicle
directly to the heart to increase the force of myocardial contraction.

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The claims stand rejected under 35 U.S.C. § 103(a) as follows:
• Claims 26-28, 35, 37, 38, 40-44, 46, and 47 based on Levy2 and
Theeuwes3 (Answer 5);
• Claim 42 based on Levy, Theeuwes, and Tuttle4 (Answer 7); and
• Claims 41 and 45 based on Levy, Theeuwes, and Fullerton5
(Answer 8).
Each of the rejections relies on the combination of Levy and
Theeuwes. The Examiner finds that Levy discloses administering agents,
including dopamine or norepinephrine, “by application of a device
comprising a polymeric matrix incorporating the antiarrhythmic agent, in a
form such as a patch or film . . . directly placed in contact with the heart
muscle at the epicardium” (Answer 5-6).
The Examiner acknowledges that Levy’s delivery device does not
include a barrier that is non-permeable to the therapeutic agent (id. at 6), but
finds that “Theeuwes teaches a drug delivery patch for delivery of a drug to
an internal organ, comprising a first layer which is impermeable to a drug
and a second layer comprising a portion that is permeable to the drug” (id.).
The Examiner concludes that it would have been obvious to modify Levy’s
device “to include the non-permeable barrier in order to achieve the
advantages taught by Theeuwes” (id. at 7); specifically, to protect the drug

2 Levy et al., US 5,387,419, issued Feb. 7, 1995.
3 Theeuwes et al., US 6,726,920 B1, issued Apr. 27, 2004.
4 Tuttle et al., US 3,987,200, issued Oct. 19, 1976.
5 Fullerton et al., Hemodynamic Advantage of Left Atrial Epinephrine
Administration After Cardiac Operations, 56 ANN. THORAC. SURG. 1263-
1266 (1993).
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from interacting with body fluids outside the target organ and limit drug loss
to the environment surrounding the organ (id. at 6).
Appellants argue that both Levy and Theeuwes teach delivery of a
drug to the entire heart, not just to a portion of the outer surface of the heart
away from the sinoatrial node, and therefore it would not have been obvious
to include a non-permeable backing layer on Levy’s device in order to limit
delivery of the drug to the pericardial fluid. Appellants have provided a
Declaration under 37 C.F.R. § 1.132 of Elazer Edelman in support of their
position.
We conclude that the Examiner has not shown that the rejections
based on Levy and Theeuwes are supported by a preponderance of the
evidence. Levy discloses a controlled release dosage form for delivering an
antiarrhythmic agent, such as dopamine or norepinephrine, which can be
attached to the heart muscle as, e.g., a patch of film (Levy, col. 3, ll. 19-45).
Levy discloses that the dosage form “is directly placed in contact with the
heart muscle [through] . . . [d]irect contact of the dosage form with the heart
muscle, either at the epicardium or the endocardium, or in some instances
through the pericardium” (id. at col. 5, ll. 41-48).
Levy states that the “antiarrhythmic agents are preferably provided in
a water soluble form, such as the hydrochloride salt of lidocaine, to facilitate
elution from the polymeric matrix material in the presence of body fluids”
(id. at col. 6, l. 67 to col. 7, l. 2). Levy discloses that an advantage of its
dosage form is that it “permits a lower dosage of antiarrhythmic agent to be
used for localized, or regional, treatment, thereby mitigating the usual
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adverse side effects of such drugs when administered systemically in doses
sufficient to be efficacious” (id. at col. 5, ll. 51-55).
As the Examiner has acknowledged, Levy does not mention including
a drug-impermeable backing layer on its dosage form. Theeuwes discloses a
drug delivery patch for delivering a drug to the surface of an internal organ,
where the patch includes a first layer that is substantially drug-impermeable,
and a second layer, disposed between the organ and the first layer, that
comprises a drug-permeable membrane that functions as a drug reservoir
(Theeuwes, col. 2, ll. 20-35). Theeuwes discloses that the drug-impermeable
layer functions “to prevent or reduce dilution of the drug contained within
the reservoir, and may limit drug loss to the environment surrounding the
target organ” (id. at col. 3, ll. 5-7).
With specific reference to the heart, Theeuwes discloses that “a drug
delivered to the outer surface of the heart can cross the pericardium, enters
the pericardial fluid, traverses the epicardium and enters cardiac tissue” (id.
at col. 6, ll. 27-30). In an exemplary embodiment, Theeuwes describes a
patch that includes a first layer that forms a sack around the heart and
substantially surrounds the heart (id. at col. 21, ll. 34-43; Figs. 7A, 7B).
Theeuwes discloses that this embodiment is “particularly useful when the
membrane surrounding the organ (e.g., a pericardial sac) is not intact” (id. at
col. 21, ll. 54-56).
Dr. Edelman declared that “both Levy and Theeuwes describe drug
delivery devices that deliver agents to the entirety of the heart” (Edelman
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Declaration,6 ¶ 7). Dr. Edelman reasons that “Levy’s matrix inherently
diffuses drug in all directions from the matrix, including into the fluid
around the heart in the pericardial sac” because Levy teaches that the drug in
its device is in a water-soluble form (id. at ¶ 8). Dr. Edelman also reasons
that, although Theeuwes discloses including a drug-impermeable layer, its
device “delivers the drug to all of the heart including the sinoatrial node.
Theeuwes does not disclose that applying a drug to only a portion of the
heart away from the sinoatrial node would be therapeutically effective.” (Id.
at ¶ 9.)
We agree with Appellants that the Edelman Declaration persuasively
shows that a person of ordinary skill in the art would have understood Levy
and Theeuwes to disclose methods of delivering a drug to the entire heart,
rather than just to a part of the heart. Levy discloses that the drug in its
device should be water-soluble to facilitate elution from the matrix “in the
presence of body fluids” (Levy, col. 7, l. 2). Levy also discloses that its
device can function by providing a drug “through the pericardium” (id. at
col. 5, ll. 41-48). These disclosures support Dr. Edelman’s conclusion that a
skilled worker would have understood Levy’s device as functioning by
releasing a drug into the pericardial fluid for delivery to the entire heart.
Theeuwes likewise discloses that its device can be attached to the
outer surface of the heart, whereby the drug enters the pericardial fluid and
is delivered to cardiac tissue (Theeuwes, col. 6, ll. 27-30). Alternatively,
when the pericardial sac is not intact, Theeuwes discloses a patch that forms

6 Declaration under 37 C.F.R. § 1.132 of Elazer R. Edelman, MD, dated
May 26, 2010.
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a sack around the heart (id. at col. 21, ll. 34-56), which would also deliver
the drug to the entire heart.
The Examiner disputes Dr. Edelman’s reading of the references, on
the basis that:
It is considered likely that, even if Levy’s patch diffuses in all
directions, the concentration which would be present in the
pericardial fluid would be negligible compared to the heart
muscle where the patch was placed, because the area covered
by the patch, as shown in Figure 7, is significantly smaller than
the entire pericardial space.
(Answer 10.)
The Examiner, however, has not provided evidence or sound technical
reasoning to support this conclusion. In particular, the Examiner has not
provided evidence that the relative sizes of the patch and the pericardial
space are important factors in determining what amount of drug is delivered
to the pericardial fluid from a patch adhered to the epicardium and exposed
to pericardial fluid.
“After evidence or argument is submitted by the applicant in response
[to the prima facie case], patentability is determined on the totality of the
record, by a preponderance of evidence with due consideration to
persuasiveness of argument.” In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir.
1992). In this case, the Examiner’s rejections are not supported by a
preponderance of the evidence of record.
SUMMARY
We reverse all of the rejections on appeal.
REVERSED
cdc