Ex parte Janoff et al.

Board of Patent Appeals and Interferences

May 30, 2001

08108822 (B.P.A.I. May. 30, 2001)

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for publication and is not binding precedent of the Board.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. 30
UNITED STATES PATENT AND TRADEMARK OFFICE
____________
BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
____________
Ex parte ANDREW S. JANOFF, MIRCEA C. POPESCU,
ALAN L. WEINER, LOIS E. BOLCSAK,
PAUL A. TREMBLAY, and CHRISTINE E. SWENSON
___________________
Appeal No. 98-2247
Application No. 08/108,822
HEARD
MAY 10, 2001
____________________________
Before KIMLIN, PAK and LIEBERMAN, Administrative Patent Judges.
LIEBERMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 from the decision of the examiner
refusing to allow claims 129, 131 and 136 through 151, which are all of the claims
pending in this application.
Appeal No. 98-2247 2
Application No. 08/108,822

THE INVENTION
The invention is directed to a method of preparing a pharmaceutical composition
wherein a salt form of an organic acid sterol derivative in an amount sufficient to form a
closed vesicle is mixed with an aqueous phase and agitated until the vesicles are formed.
The mixture is essentially free of organic solvent. Other features of the claimed subject
matter are set forth in the following illustrative claim.

THE CLAIMS
Claims 129 is illustrative of appellants’ invention and is reproduced below.
129. A method for preparing a pharmaceutical composition which comprises liposomes
having bilayers comprising a lipid which consists essentially of a salt form of an organic
acid sterol derivative capable of forming closed bilayers, the method comprising:
(I) mixing an amount of the salt form of the organic acid sterol derivative sufficient
to form closed vesicles with an aqueous phase so as to form a mixture comprising the
aqueous phase and the sterol derivative, wherein the mixture is essentially free of organic
solvent; and
(ii) agitating the mixture until vesicles are formed,
wherein when the sterol derivative is negatively charged at neutral pH the mixture
is substantially free of multivalent cations or when the derivative is positively charged at
neutral pH the mixture is substantially free of multivalent anions.

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Application No. 08/108,822
On the record before us it is clear that the statement of the rejection is directed to claim 129 not claim1
120. Claim 120 was canceled in the amendment dated September 25, 1995. In addition reference to the
THE REFERENCES OF RECORD
As evidence of obviousness, the examiner relies upon the following references.
Panzarella 3,197,367 July 27, 1965
Klein 3,859,047 Jan. 7, 1975
James E. F. Reynolds (ed.), Martindale The Extra Pharmacopoeia, pp. 726-727 (28th
ed., The Pharmaceutical Press, London, 1982).
Marc J. Ostro (ed.), Liposomes, pp. 29-39 (Marcel Dekker, Inc., New York, 1983).
THE REJECTIONS

Claims 129, 131, 137 through 145 and 150 stand rejected under 35 U.S.C.
§ 103(a) as being unpatentable over Ostro in view of Klein.
Claim 136 stands rejected under 35 U.S.C. § 103(a) as being unpatentable over
Ostro in view of Klein and further in view of Martindale.
Claims 147, 149 and 151 stand rejected under 35 U.S.C. § 103(a) as being
unpatentable over Ostro in view of Klein and further in view of Panzarella.
Claims 120 [sic.,129], and 137 through 151 stand rejected under 35 U.S.C.
§ 112, second paragraph, as being indefinite for failing to particularly point out and
distinctly claim the subject matter which appellants regard as the invention. 1
Appeal No. 98-2247 4
Application No. 08/108,822
Answer, pages 3 and 8 in conjunction with the appellants supporting statement at Oral Hearing necessarily leads
us to conclude that the independent claim at issue in the rejection under the second paragraph of 35 U.S.C. §
112 is claim 129, not claim 120.

OPINION
We have carefully considered all of the arguments advanced by the appellants and
the examiner and agree with the appellants that the rejections of claims 129, 131 and
136 through 151, are not well founded. Accordingly, we reverse each of the rejections.
The Rejection under 35 U.S.C. §112, Second Paragraph
“The legal standard for definiteness under the second paragraph of 35 U.S.C.
§ 112 is whether a claim reasonably apprises those of ordinary skill in the art of its
scope.” In re Warmerdam, 33 F.3d 1354, 1361, 31 USPQ2d 1754, 1759 (Fed. Cir.
1994). The inquiry is to determine whether the claim sets out and circumscribes a
particular area with a reasonable degree of precision and particularity. The definiteness
of the language employed in a claim must be analyzed not in a vacuum, but in light of the
teachings of the particular application. In re Moore, 439 F.2d 1232, 1235, 169 USPQ
236, 238 (CCPA 1971).
It is the examiner’s position that the claimed subject matter is indefinite in “not
reciting that the aqueous phase contains a bioactive agent in the event that the salt-
forming base is not itself a bioactive agent.” See Answer, page 8. In our view, the
examiner’s submission is directed to the broudness of the claimed subject matter as
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Application No. 08/108,822
opposed to the definiteness of the claimed subject matter.
However, it is well settled that breadth does not necessarily render a claim
indefinite and the examiner has stated no other ground of rejection. In re Gardner, 427
F.2d 786, 788, 166 USPQ 138, 140 (CCPA 1970) (“Breadth is not indefiniteness.”);
In re Borkowski, 422 F.2d 904, 909, 164 USPQ 642, 645-46 (CCPA 1970).
Furthermore, we find that the description in the specification, page 17,
provides for the addition of a water soluble compound to previously formed liposomes in
at least one disclosed embodiment. Therefore, liposomes may be prepared in the
absence of a water soluble compound, such as a bioactive agent, which agent is not a
necessary element as alleged on the record before us. Accordingly, the claimed subject
matter directed to the formation of a liposome in the absence of a water soluble
compound, such as a bioactive agent, is not indefinite
On this record, we conclude that the specification provides a reasonable standard
for understanding the metes and bounds of the claimed subject matter, when the claims
are read in light of the specification. Seattle Box Co. v. Industrial Crating & Packing, Inc,
731 F.2d 818, 826, 221 USPQ 568, 573-574 (Fed. Cir. 1983). Accordingly, we
reverse the rejection of the examiner.
The Rejection under 35 U.S.C. § 103
“[T]he examiner bears the initial burden, on review of the prior art or on any
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Application No. 08/108,822
A liposome is defined as an artificial vesicle composed of one or more concentric phospholipid2
bilayers. See Webster's Ninth New Collegiate Dictionary, page 696, Merriam-Webster Inc. Springfield, MA
1986.
other ground, of presenting a prima facie case of unpatentability,” whether on the
grounds of anticipation or obviousness. In re Oetiker, 977 F.2d 1443, 1445, 24
USPQ2d 1443, 1444 (Fed. Cir. 1992). On the record before us, the examiner relies
upon four separate rejections to establish a prima facie case of obviousness. Each of the
four rejections however, are directed to a single premise. It is the position of the
examiner that, “it would have been obvious at the time the applicants’ invention was
made to use one of the stated salts shown to be old by Klein (abstract; Ex’s 1 - 4) in lieu
of, or in addition to, the phospholipids in the methods of Ostro to produce steroidal
liposomes.” See Answer, pages 5 and 6. We disagree.
The examiner has relied upon Ostro as the primary reference in each of the
rejections under Section 103. Ostro discloses a plurality of methods for the preparation
of liposomes. See pages 33 to 39. The methods include preparing the liposomes either2
in the presence of organic solvent or in the absence of organic solvent. We find that the
preparation of small unilamellar vesicles occurs in the absence of organic solvent. See
page 33. Similarly, we find that multilamellar vesicles are prepared in the absence of
organic solvent. See page 36 and 37. Alternately organic solvent may be present during
the formation of vesicles. See pages 38 and 39.
Ostro however, is silent as to which lipids may be used to form liposome vesicles.
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Application No. 08/108,822
See Webster’s Third New International Dictionary, p. 1318 G. & C. Merriam Co., 1971.3
The sole relevant statement in this respect found in Ostro is that, “[t]he lipid is not
necessarily phospholipid but this is the most commonly used component.” See page 28.
The examiner however, apparently interprets the statement in Ostro as providing for the
utilization of any lipid in liposome formation. Accordingly, the examiner concludes that
the disclosure of appellants’ preferred lipid by Klein is sufficient to establish a prima facie
case of obviousness.
In reaching that conclusion, however, the record before us is necessarily based
upon several unsupported assumptions. Initially, it is requisite that lipids in general are
able to form liposomes. On this record, that fact has not been established. It is further
assumed on the record that the cholesteryl hemisuccinate disclosed by Klein is a lipid.
Klein however, never states that cholesteryl hemisuccinate is a lipid.
Moreover, lipids have been defined in part as “[a]ny of a group of substances
that generally are soluble in ether, chloroform or other solvents for fats, but are only
sparingly soluble in water.” In contrast, although Klein discloses a preferred sterol salt3
of the claimed subject matter, cholesteryl hemisuccinate, we find that Klein describes
cholesteryl hemisuccinate as a water soluble cholesterol salt. See Abstract, column 2,
lines 6-8, 42-52, and 68 through column 3, line 1. Accordingly, on this record, the
examiner fails to establish as a fact that the cholesteryl hemisuccinate is a lipid.
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Application No. 08/108,822
It is well settled that it is the examiner who has the burden of establishing that one
of ordinary skill in the art would have found the requisite motivation and reasonable
expectation of success for the proposed modification from the applied prior art teachings.
See In re Vaeck, 947 F.2d 488, 493, 20 USPQ2d 1438, 1442 (Fed. Cir. 1991). It is
reasonable to conclude based upon the above findings that there is neither a suggestion
in the art of record to utilize the cholesteryl hemisuccinate of Klein to form a liposome,
nor a reasonable expectation of success was fully employing cholesterol derivative of
Klein in liposome formation.
Finally, the references to both Martindale and Panzarella are directed to limitations
present in dependent claims, but do not remedy the deficiencies discussed above.
Accordingly, the rejections of the examiner are reversed.

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Application No. 08/108,822
Decision
The rejection of claims 129, 131, 137 through 145 and 150 under 35 U.S.C.
§ 103(a) as being unpatentable over Ostro in view of Klein is reversed.
The rejection of claims 136 under 35 U.S.C. § 103(a) as being unpatentable over
Ostro in view of Klein and further in view of Martindale is reversed.
The rejection of claims 147, 149 and 151 under 35 U.S.C. § 103(a) as being
unpatentable over Ostro in view of Klein and further in view of Panzarella is reversed.
The rejection of claims 120 [sic] [129], and 137 through 151 under 35 U.S.C.
§ 112, second paragraph, as being indefinite for failing to particularly point out and
distinctly claim the subject matter which appellants regard as the invention is reversed.

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Application No. 08/108,822

The decision of the examiner is reversed.
REVERSED
EDWARD C. KIMLIN )
Administrative Patent Judge )
)
)
)
)
) BOARD OF PATENT
CHUNG K. PAK ) APPEALS
Administrative Patent Judge ) AND
) INTERFERENCES
)
)
)
)
PAUL LIEBERMAN )
Administrative Patent Judge
)
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Application No. 08/108,822
ROSANNE GOODMAN
THE LIPOSOME COMPANY, INC.
ONE RESEARCH WAY
PRINCETON FORRESTAL CENTER
PRINCETON , NJ 08540