Ex Parte Takle et al

Board of Patent Appeals and Interferences

Dec 23, 2002

08616141 (B.P.A.I. Dec. 23, 2002)

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for publication and is not binding precedent of the Board.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. 25

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte GARRY B. TAKLE and SHAJI T. GEORGE
__________

Appeal No. 2001-17051
Application No. 08/616,141
__________

ON BRIEF
__________

Before WINTERS, SCHEINER, 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 1-8, 11-13, and 19-31. Claims 9 and 10 are
free from rejection, and the examiner indicated (Answer, page 2) that claims 14-
18 are allowable.
Claim 19 is illustrative of the subject matter on appeal and is reproduced
below:
19. A composition for delivering a compound having a net negative
charge to cells comprising
a. a compound having a net negative charge ionically bound to a
macrocycle having a net positive charge selected from the
group consisting of natural porphyrins, natural phthalocyanins,
synthetic porphyrins, synthetic phthalocyanins, and conjugates

1 This appeal is related to Appeal No. 2001-1498 (Application No. 08/912,378) accordingly we
have considered these two appeals together.
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Application No. 08/616,141

thereof, in an amount effective to enhance delivery of the
compound to cells preferentially binding the macrocycle, and

b. a pharmaceutically acceptable carrier for pharmaceutical
administration.

Claim 1 is drawn to a method of using the compound-macrocycle mixture.
In addition, various dependent claims further limit the macrocycle to porphyrin,
which may have antiviral activity including, as set forth in claim 26, anti-hepatitis
B activity.
The references relied upon by the examiner are:
Dixon et al. (Dixon) 5,192,788 Mar. 09, 1993
Leonetti et al. (Leonetti) “Antibody-Targeted Liposomes Containing
Oligodeoxyribonucleotides Complementary to Viral RNA Selectively inhibit Viral
Replication,” Proc. Natl. Acad., Sci., Vol. 87 pp. 2448-2451 (1990)

Doan et al. (Doan) “Sequence-Targeted Chemical Modification of Nucleic Acids
by Complementary Oligonucleotides Covalently Linked to Porphyrins,”
Nucleic Acids Research, Vol. 15, No. 21 pp. 8643-8658 (1987)

Korba et al. (Korba) “Use of a Standardized Cell Culture Assay to Assess
Activities of Nucleoside Analogs Against Hepatitis B Virus Replication,”
Antiviral Research, Vol. 19 pp. 55-70 (1992)

Lisziewicz et al. (Lisziewicz) “Specific inhibition of human immunodeficiency virus
type 1 replication b antisense oligonucleotides : An in vitro model for treatment,”
Proc. Natl. Acad. Sci., Vol. 89 pp. 11209-11213 (1992)

Yuan et al. (Yuan) “Targeted Cleavage of mRNA by Human Rnase P,”
Proc. Natl. Acad. Sci, Vol. 89 pp. 8006-8010 (1992)

Cannon, “Pharmaceutics and Drug Delivery Aspects of Heme and Porphyrin
Therapy,” Journal of Pharmaceutical Sciences, Vol. 82,
No. 5 pp. 435-446 (1993)

Offensperger et al. (Offensperger) “In vivo Inhibition of Duck Hepatitis B Virus
Replication and Gene Expression by Phosphorothioate Modified Antisense
Oligodeoxynucleotides,” The EMBO Journal. Vol. 12, No. 3 pp. 1257-1262
(1993)

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Application No. 08/616,141

Yu et al. (Yu) “A Hairpin Ribozyme Inhibits Expression of Diverse Strains of
Human Immunodeficiency Virus Type 1,” Proc. Natl. Acad. Sci, Vol. 90
pp. 6340-6344 (1993)

GROUNDS OF REJECTION
Claim 31 stands rejected under 35 U.S.C. § 112, first paragraph, as being
based on an insufficient disclosure to support or enable the claimed invention.
Claims 1, 2, 5, 6, 19, 20, 23 and 30 stand rejected under 35 U.S.C.
§ 102(b) as anticipated by Cannon
Claims 1-8, 11, 12, 19-25 and 31 stand rejected under 35 U.S.C. § 103 as
being unpatentable over Dixon in view of any one of Yu, Leonetti or Lisziewicz.
Claims 1-8, 11-13, 19-24 and 31 stand rejected under 35 U.S.C. § 103 as
being unpatentable over Doan and Offensperger.
Claims 26-29 stand rejected under 35 U.S.C. § 103 as being unpatentable
over Dixon, Yuan, Offensperger and Korba.
We reverse.
DISCUSSION
THE REJECTION UNDER 35 U.S.C. § 112, FIRST PARAGRAPH:
To satisfy the enablement requirement of 35 U.S.C. § 112, first
paragraph, a patent application must adequately disclose the claimed invention
so as to enable a person skilled in the art to practice the invention at the time the
application was filed without undue experimentation. Enzo Biochem, Inc. v.
Calgene, Inc., 188 F.3d 1362, 1371-72, 52 USPQ2d 1129, 1136
(Fed. Cir. 1999). We note, however, that “nothing more than objective
enablement is required, and therefore it is irrelevant whether this teaching is
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Application No. 08/616,141

provided through broad terminology or illustrative examples.” In re Marzocchi,
439 F.2d 220, 223, 169 USPQ 367, 369 (CCPA 1971). As set forth in In re
Wright, 999 F.2d 1557, 1561-62, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993):
When rejecting a claim under the enablement requirement of
section 112, the PTO bears an initial burden of setting forth a
reasonable explanation as to why it believes that the scope of
protection provided by that claim is not adequately enabled by the
description of the invention provided in the specification of the
application; this includes, of course, providing sufficient reasons for
doubting any assertions in the specification as to the scope of
enablement.

As the examiner recognizes (Answer, page 5), “[c]laim 31 recites
dissociation of the macrocycle from the compound after internalization inside the
cells.” As we understand the examiner’s position, since “page 6, lines 9-12 [of
the specification], provides support for internalization of the complex within cells,
but not for dissociation of the complex”, the specification fails to enable the
claimed invention.
Lines 9-12, on page 6 of appellants’ specification state “the compound to
be delivered is ionically bound to the macrocyclic compound until it and the
bound nucleic acids are internalized in the targeted cells [emphasis added].”
According to appellants (Reply Brief, page 3), “[t]he critical term in this passage
[is] – ‘until’ ….” This language, absent factual evidence to the contrary, is
sufficient to objectively enable the claimed invention. Marzocchi.

What is missing from the examiner’s rejection is factual evidence
disputing appellants’ objectively enabled specification. It is the examiner’s
burden to make out a case of non-enablement. In our opinion, the examiner has
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Application No. 08/616,141

not met her burden on this record. Accordingly, we reverse the rejection of claim
31 under 35 U.S.C. § 112, first paragraph.
THE REJECTION UNDER 35 U.S.C. § 102:
The following quote represents the examiner’s entire statement of
rejection under 35 U.S.C. § 102(b). “Claims 1, 2, 5, 6, 19, 20, 23, and 30 stand
rejected under 35 U.S.C. [§] 102(b) as being anticipated by Cannon.” Answer,
page 5. In responding to appellants’ arguments (Answer, page 8), the examiner
finds:
[t]he instant claims are drawn to compositions comprising a
compound having a net negative charge ionically bound to a
macrocycle (porphyrin) having a net positive charge and to
methods of delivering compounds having a net negative charge to
cells comprising mixing the compound with a macrocycle having a
net positive charge, wherein the macrocycle ionically binds to the
compound.

Conspicuous in its absence in this statement, and the statement of the
rejection, is any explanation as to why the amounts in Cannon would be effective
to enhance delivery of the compound to cells that bind the macrocycle, as is
required by the claimed invention. While the examiner argues (Answer, page 9),
“[t]he method of Cannon has the same active steps as the claimed method i.e.
the mixing together of a negatively charged compound (lipid) with a positively
charged macrocycle … and the delivery of the mixture to cells” the examiner fails
to explain where Cannon teaches an amount that is effective to enhance delivery
of the compound to cells as is required by the claimed invention.
“Under 35 U.S.C. § 102, every limitation of a claim must identically appear
in a single prior art reference for it to anticipate the claim.” Gechter v. Davidson,
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Application No. 08/616,141

116 F.3d 1454, 1457, 43 USPQ2d 1030, 1032 (Fed. Cir. 1997). “Every element
of the claimed invention must be literally present, arranged as in the claim.”
Richardson v. Suzuki Motor Co., Ltd., 868 F.2d 1226, 1236, 9 USPQ2d 1913,
1920 (Fed. Cir. 1989). Since Cannon fails to teach an amount of a macrocycle
effective to enhance delivery of the compound to the cells, Cannon fails to
anticipate the claimed invention. Accordingly, we reverse the rejection of claims
1, 2, 5, 6, 19, 20, 23, and 30 under 35 U.S.C. § 102(b) as being anticipated by
Cannon.
THE REJECTIONS UNDER 35 U.S.C. § 103:
The combination of Dixon in view of any one of Yu, Leonetti or Lisziewicz:
The examiner finds (Answer, page 5), Dixon “disclose that certain
porphyrins inhibit the reverse transcriptase of HIV-1.” In addition, the examiner
finds (Answer, page 6), that each of Yu, Leonetti and Lisziewicz “is concerned
with inactivation of HIV-1 through the use of oligonucleotides.” Based on these
findings, the examiner concludes (id.), “[i]t would have been prima facie obvious
… to have combined the antiviral porphyrins described by Dixon ... with the
antiviral oligonucleotides taught by Yu …, Leonetti …, or Lisziewicz … for an
improved multi-drug antiviral treatment regimen.” In responding to appellants’

arguments the examiner makes reference (Answer, page 11) to In re Kerkhoven,
626 F.2d 846, 205 USPQ 1069 (CCPA 1980) for the proposition that “[i]t is prima
facie obvious to combine two compositions each of which is taught by the prior
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Application No. 08/616,141

art to be useful for the same purpose, in order to form a third composition to be
used for the very same purpose.”
In addition, the examiner finds (id.) “it would be expected that ionic
bonding would enhance the stability of both the compound and the porphyrin in
vivo, as is suggested in Cannon….” For the following reasons we are unable to
agree with the examiner’s position. As set forth in In re Hoch, 428 F.2d 1341,
1342 n.3, 166 USPQ 406, 407 n.3 (CCPA 1970), “[w]here a reference is relied
on to support a rejection, whether or not in a ‘minor capacity,’ there would appear
to be no excuse for not positively including the reference in the statement of the
rejection”, accordingly the examiner’s reliance on Cannon is inappropriate, and
we do not include the teachings of Cannon as part of our deliberations on this
issue. Furthermore, it appears that the examiner’s position is that ionic bonding
would inherently enhance the stability of both the compound and the porphyrin.
Inherency, however, is immaterial if, as here, one or ordinary skill in the art would
not appreciate or recognize that inherent result. In re Shetty, 566 F.2d 81,
86, 195 USPQ 753, 756 (CCPA 1977).
Stated differently, none of the references relied upon by the examiner
recognize that ionic bonding would enhance the stability of both the porphyrin
and the oligonucleotides. In addition, the combination of references also fails to
suggest an amount of macrocycle effective to enhance delivery of the
oligonucleotides to cells binding the macrocycle. See e.g., Brief, pages 12-13.
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Application No. 08/616,141

For these reasons, it is our opinion that the examiner failed to meet her burden2
of providing the evidence necessary to support a prima facie case of
obviousness. Accordingly, we reverse the rejection of claims 1-8, 11, 12, 19-25
and 31 under 35 U.S.C. § 103 as being unpatentable over Dixon in view of any
one of Yu, Leonetti or Lisziewicz.
The combination of Doan and Offensperger:
The examiner finds (Answer, page 6), Doan, “describe oligonucleotide
porphyrin conjugates.” In addition, the examiner finds (id.), Offensberger
“describe in vivo inhibition of HBV replication wherein antisense oligonucleotides
are employed.” Based on this evidence, the examiner concludes (id.), “[i]t would
have been prima facie obvious to … produced porphyrin-anti-HBV antisense
oligonucleotide complexes with the reasonable expectation of inhibiting HBV
replication.”
As appellants point out (Brief, page 14), in contrast to the claimed
invention which requires an ionic bond between the porphyrin and the compound
(oligonucleotide), Doan teach covalently linking an oligonucleotide to a porphyrin
ring. In responding to appellants’ argument, it appears that the examiner shifts
horses and emphasizes (Answer, pages 12-13) that Offensperger:
also teach encapsidation of the oligonucleotiedes into liposomes
for enhanced stability and delivery to target cells and thus provides
the suggestion and motivation to ionically bind the porphyrin with a
negatively charged compound by teaching enhanced stability and
delivery to target cells when the porphyrin is ionically bound to a
lipid.

2 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).
Appeal No. 2001-1705 Page 9
Application No. 08/616,141

However, as appellants point out (Reply Brief, page 5), “Offensperger et al.
actually discloses inclusion of a cell surface receptor ligand in a liposome
containing an oligonucleotide. This is not what is claimed and does not suggest
the presently claimed ionic complexes.”
It is well-established that before a conclusion of obviousness may be
made based on a combination of references, there must have been a reason,
suggestion or motivation to lead an inventor to combine those references.
Pro-Mold and Tool Co. v. Great Lakes Plastics Inc., 75 F.3d 1568, 1573,
37 USPQ2d 1626, 1629 (Fed. Cir. 1996). On this record we find no suggestion
to modify the teachings of Doan with those of Offensperger to obtain the claimed
invention which, as appellants point out, require ionic complexes. Accordingly,
we reverse the rejection of claims 1-8, 11-13, 19-24 and 31 under 35 U.S.C.
§ 103 as being unpatentable over Doan and Offensperger.
The combination of Dixon, Yuan, Offensperger and Korba:
The examiner finds (Answer, pages 6-7), Dixon, “teach that certain
porphyrins inhibit HIV-1”; Offensberger “describe in vivo inhibition of HBV by
antisense oligonucleotides”; Korba “disclose routing testing methods for
determining if a compound has activity against HBV”; and Yuan “disclose the
parameters necessary for EGS [external guide sequences] in eukaryotic cells.”
However, as discussed supra, we find no suggestion to modify the
teachings of Doan with those of Offensperger to obtain the claimed invention
which, as appellants point out, require ionic complexes. Yuan and Korba fail to
make up for the deficiencies in the combination of Doan and Offensperger.
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Application No. 08/616,141

Accordingly, we reverse the rejection of claims 26-29 under 35 U.S.C. § 103 as
being unpatentable over Dixon, Yuan, Offensperger and Korba.
REVERSED

Sherman D. Winters )
Administrative Patent Judge )
)
)
) BOARD OF PATENT
Toni R. Scheiner )
Administrative Patent Judge ) APPEALS AND
)
) INTERFERENCES
)
Donald E. Adams )
Administrative Patent Judge )

DA/dym

Appeal No. 2001-1705 Page 11
Application No. 08/616,141

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