Ex parte Barenholz et al.

Board of Patent Appeals and Interferences

Sep 29, 2000

08257866 (B.P.A.I. Sep. 29, 2000)

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publication and is not binding precedent of the Board.

Paper No. 19

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte YECHEZKEL BARENHOLZ,
AND HILARY SHMEEDA
__________

Appeal No. 1997-0661
Application No. 08/257,866
__________

ON BRIEF
__________

Before, WINTERS, WILLIAM F. SMITH, and ADAMS, Administrative Patent
Judges.

ADAMS, Administrative Patent Judge.

DECISION ON APPEAL

This is a decision on the appeal under 35 U.S.C. § 134 from the examiner’s
final rejection of claims 1-5, which are all the claims pending in the application.
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Application No. 08/257,866

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Claim 1 is illustrative of the subject matter on appeal and is reproduced
below:

1. A method for treating hypertension in a subject having elevated blood
pressure, comprising:
intravenously administering to the subject a suspension of small
unilamellar liposomes composed primarily of phosphatidylcholine
phospholipids having phase transition temperatures in the range between
about -10 and 37ºC, and
repeating said administering over a period of at least several days
and in an amount effective to produce a reduction in both systolic and
diastolic blood pressure of at least 10 percent from said elevated blood
pressure.

The references relied upon by the examiner are:
Barenholz et al. (Barenholz) 4,812,314 Mar. 14, 1989
Soloviev et al. (Soloviev) 1, “Phospholipid vesicles (liposomes) restore endothelium-
dependent cholinergic relaxation in thoracic aorta from spontaneously hypertensive
rats,” J. Hypertension, Vol. 11(6), pp.623-627 (1993)

GROUND OF REJECTION
Claims 1-52 are rejected under 35 U.S.C. § 103 as obvious over Soloviev in
view of Barenholz.
We reverse.

1 We note that the examiner makes reference (Answer, page 3) to the entire
Soloviev reference. However, upon review of the administrative file we note the
Notice of References Cited, FORM PTO-892, attached to Paper No. 5. The Notice
of References Cited refers to “CA 119:173862m Soloviev et al., 1993.” Indeed the
only Soloviev reference in the administrative file is the Chemical Abstract. We have
however, obtained a copy of the entire Soloviev reference and will base our
decision on Soloviev as read in its entirety.
2 We note appellants canceled claim 6 in the amendment filed under 37 CFR
§ 1.116 (Paper No. 11, received October 5, 1995).
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DISCUSSION
In reaching our decision in this appeal, we have given careful consideration
to the appellants’ specification and claims, and to the respective positions
articulated by the appellants and the examiner. We make reference to the
examiner’s Answer3 for the examiner’s reasoning in support of the rejection. We
further reference appellants’ Brief4, and appellants’ Reply Brief5 for the appellants’
arguments in favor of patentability.
THE REJECTION UNDER 35 U.S.C. § 103:
The initial burden of presenting a prima facie case of obviousness rests on
the examiner. In re Oetiker, 977 F.2d 1443, 1445, 24 USPQ2d 1443, 1444 (Fed.
Cir. 1992).
The examiner states (Answer, bridging paragraph, pages 3-4) that “Soloviev
disclose that liposomes made of egg phosphatidylcholine had a relaxing effect on
the thoracic aortas of spontaneously hypertensive rats.” The examiner therefore
concludes that:
To administer the liposomes for the treatment of hypertension would
have been obvious from the disclosure of Soloviev et al. as the
liposomes had a relaxing effect on the aortic smooth muscle. Thus by
relaxing blood vessels the pressure in the blood vessel would go
down as the diameter of the vessel increased. Thus a substance
known to relax blood vessels would logically be presumed to be useful
in the treatment of hypertension.

3 Paper No. 16, mailed April 24, 1996.
4 Paper No. 15, received March 6, 1996.
5 Paper No. 17, received June 27, 1996.
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Application No. 08/257,866

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The examiner relies upon Barenholz to teach liposomes of between 0.02 and
0.08 microns in size.
Appellants argue (Brief, page 5) that the “Soloviev reference would not give
one of ordinary skill in the art a reasonable expectation of success for treating
hypertension by the intravenous administration of liposomes.” Reading Soloviev in
its entirety, W.L. Gore & Assocs., Inc. v. Garlock, Inc., 721 F.2d 1540, 1550, 220
USPQ 303, 311 (Fed. Cir. 1983), cert. denied, 469 U.S. 851 (1984), Soloviev teach
(page 624, column 1) preconstricting thoracic aortic rings to plateau level in vitro
with noradrenaline, and then administering acetylcholine to relax the noradrenaline-
preconstricted ring. Soloviev found (page 625,
figure 2) that administering liposomes can further relax the acetylcholine relaxed
noradrenaline-preconstricted ring. However, Soloviev also teach (page 625,
column 1) that “liposomes administered at plateau level of noradrenaline-induced
contraction caused increased tension development in both [Wistar-Kyoto and
spontaneously hypertensive] strains of rats but never relaxation.”
Appellants note (Reply Brief, page 2) that “[c]laim 1 on appeal requires a
decrease of systolic and diastolic blood pressure of at least 10 percent in the
subject, whereas Soloviev did not measure blood pressure change as a result of
treatment.” Here, we agree with appellants, Soloviev does not provide a
reasonable expectation of success in obtaining a “reduction in both systolic and
diastolic blood pressure of at least 10 percent from said elevated blood pressure”
by administering a suspension of small unilamellar liposomes intravenously, as
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Application No. 08/257,866

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required in claim 1. In re O’Farrell, 858 F.2d 894, 904, 7 USPQ2d 1673, 1681
(Fed. Cir. 1988) (obviousness also requires a “reasonable expectation of
success”).
As recognized by appellants (Brief, page 6) “[t]he deficiencies of Soloviev
are not made up for by the teachings of Barenholz.” Barenholz is directed to
(Abstract) “[a] method of treating a relatively aged animal to reverse age-related
changes in the lipid composition of organ and tissue cells, such as heart muscle
cells.” We agree with appellants (Brief, page 6) that “Barenholz provides no basis
for predicting that intravenously administered liposomes would be effective in
lowering arterial pressure in a subject suffering from hypertension.”
In our opinion, the examiner failed to meet her burden of establishing a
prima facie case of obviousness. In re Oetiker, 977 F.2d at 1445, 24 USPQ2d at
1444 (Fed. Cir. 1992). Having determined that the examiner has not established a
prima facie case of obviousness, we find it unnecessary to discuss the Guyton6 and
Gabazon et al.7 references relied on by appellants (Brief, page 7) to rebut any such
prima facie case.

6 Textbook of Medical Physiology, 269 (7th ed. 1986).

7 “Liposomes as In Vivo Carriers of Adriamycin: Reduced Cardiac Uptake and
Preserved Antitumor Activity in Mice,” Cancer Research, Vol. 42, pp. 4734-4739
(1982).
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Where the examiner fails to establish a prima facie case, the rejection is
improper and will be overturned. In re Fine, 837 F.2d 1071, 1074, 5 USPQ2d 1596,
1598 (Fed. Cir. 1988). Accordingly, we reverse the rejection of claims 1-5 under 35
U.S.C. § 103 over Soloviev in view of Barenholz.

REVERSED

)
Sherman D. Winters )
Administrative Patent Judge )
)
)
) BOARD OF PATENT
William F. Smith )
Administrative Patent Judge ) APPEALS AND
)
) INTERFERENCES
)
Donald E. Adams )
Administrative Patent Judge )
Appeal No. 1997-0661
Application No. 08/257,866

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