Ex Parte Smith

Board of Patent Appeals and Interferences

Jul 25, 2006

08472801 (B.P.A.I. Jul. 25, 2006)

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for publication and is not binding precedent of the Board.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 LARRY J. SMITH
__________

Appeal No. 2006-0865
Application No. 08/472,801
__________

HEARD: May 9, 2006
__________

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 7, 8, 41, 45, 46, 48, 53, 74, 88, 91, 92 and 96-100. Claims 1-6, 9-
40, 42-44, 47, 49-52, 54-73, 75-87, 89, 90 and 93-95 have been withdrawn from
consideration.
Claim 7 is representative and reads as follows:
7. A method for rational discovery of antisense oligonucleotides useful as
therapeutics for the treatment of an Aberrant Programming Disease wherein said
Aberrant Programming Disease is cancer, comprising the steps of (i) selecting one or
more transcriptional regulator gene targets implicated in the regulation of cellular
programming, said transcriptional regulator targets are not oncogenes and are
expressed by cancer cells to be reprogrammed; (ii) selecting one or more prototype
antisense oligonucleotides(s) to target transcripts of the selected non-oncogene
transcriptional regulators, where said prototype antisense oligonucleotide(s) is selected
from the group of oligonucleotides comprising SEQ ID NO: 1 through SEQ ID NO: 3626;
(iii) evaluating said prototype antisense oligonucleotide(s) in a Reprogramming Test,
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alone and then in combination with an augmentation agent, for capacity to
therapeutically reprogram the Aberrant Programmed disease cells while not adversely
reprogramming normal cells, said augmentation agent being capable of altering the
pattern of transcriptional regulator expression in the Aberrant Programmed disease
cells; (iv) selecting sequence- and length-variants of prototype oligonucleotides scored
in the Reprogramming Test to exhibit capacity to reprogram Aberrant Programming
cells; (v) evaluating said variants for efficacy in the Reprogramming Test, either alone
or in combination with the appropriate augmentation agent; (vi) selecting the most active
of the evaluated antisense oligonucleotides, or antisense oligonucleo-tide/augmentation
agent combination, and testing the same in vivo for efficacy.

The prior art references cited by the examiner are:

Bayever et al., (Bayever), “Systemic Administration of a Phosphorothioate
Oligonucleotide with a Sequence Complementary to p53 for Acute Myelogenous
Leukemia and Myolodysplastic Syndrome: Initial Results of a Phase I Trial,” Antisense
Research and Development, Vol. 3, pp. 383-390 (1993)

Branch, “A good antisense molecule is hard to find,” TIBS, Vol. 23, pp. 45-50 (1998)

Bishop et al., (Bishop), “Phase I Trial of an Antisense Oligonucleotide OL(1)p53 in
Hematologic Malignancies,” J. Of Clinical Oncology, Vol. 14, No. 4, pp. 1320-1326
(1996)

Yuen et al., (Yuen), “Clinical Studies of Antisense Therapy in Cancer,” Frontiers in
Bioscience , pp. d588-593 (2000)

Barton et al., (Barton), “Antisense oligonucleotides directed against p53 have
antiproliferative effects unrelated to effects on p53 expression,” British Journal of
Cancer, Vol. 71, pp. 429-437 (1995)

Grounds of Rejection

Claims 7, 8, 41, 45, 46, 48, 53, 74, 88, 91, 92 and 96-100 stand rejected under
35 U.S.C. §112, first paragraph for lack of enablement
We reverse this rejection.

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DISCUSSION
Background
According to appellant (Brief, pages 2-3)

The present invention is based on methods for screening antisense
oligonucleotides useful for the treatment of Aberrant Programming (AP)
diseases. … [T]he basic disease causing entity in AP diseases is a
specific type of relational alteration among certain cellular components
involved in cellular programming control where the key programs involved
viability (apoptosis or programmed cell death), proliferation and
differentiation. …In one embodiment …transcription regulator genes are
used as target genes for designing and selecting antisense
oligonucleotides as therapeutics for the treatment of an AP disease, e.g.,
cancer. An exemplary method includes the selection of a non-oncogene
transcriptional regulator (TR) gene which is expressed in the diseased
cells and implicated in the regulation of cellular programming; the selection
of antisense oligonucleotides corresponding to the selected non-oncogene
TR gene among the oligonucleotides with SEQ ID NOS. 1-3626 (Table
XIX); and the evaluation of the selected antisense oligonucleotides alone
and then in combination with augmentation agents in a Reprogramming
Test. …

Enablement

Claims 7, 8, 41, 45, 46, 48, 53, 74, 88, 91, 92 and 96-100 stand rejected under
35 U.S.C. §112, first paragraph for lack of enablement.
According to the Examiner (Answer, pages 5-6)
The instant specification[ ] offers sequences (SEQ ID NOS: 1-3626)
as "prototype antisense oligonucleotides" for evaluation by the instant
methods. Many of these prototype are targeted to genes that have not
even been associated with cancer. The claims are drawn to the use of
these "prototypes", which were obtained by computer analysis of nucleic
acid folding (the "Tertiary Selection Method["]), where these
oligonucleotides are tested in a "Reprogramming Test" alone or in
combination with an "augmentation agent". … The art of antisense
oligonucleotide selection and design for therapy is an unpredictable art
where the rational selection of antisense oligonucleotides for therapy is
doubted…[I]t is not yet clear whether in vitro screening techniques. . . will
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identify ODNS that are effective in vivo.…

Essentially, the examiner argues the claimed screening techniques are not
enabled because it is not clear that any antisense oligonucleotides will function as a
therapy with any predictability and that “one of skill in the art is left to perform undue trial
and error empirical search for antisense oligonucleotides where the instant specification
fails to provide any correlation with the ‘prototype antisense oligonucleotides’”. Answer,
page 7.
In reply, appellant argues “[a]pplicants are claiming fully described methods for
identification of antisense oligonucleotides useful for the treatment of AP disease” and,
“the skilled person is not reduced to trial and error to practice the invention as claimed.”
Brief, page 19.
Before we address the enablement issue, we note that language in a claim
preamble acts as a claim limitation only when such language serves to “give meaning to
a claim and properly define the invention,” not when the preamble merely states a
purpose or intended use of the invention. In re Paulsen, 30 F.3d 1475, 1479, 31
USPQ2d 1671, 1673 (Fed. Cir. 1994) (quoting DeGeorge v. Bernier, 768 F.2d 1318,
1322 n.3, 226 USPQ 758, 766 n.3 (Fed. Cir. 1985)). In our view, the preamble claim
language “useful as therapeutics for the treatment of an Aberrant Programming
Disease” is a recitation of the intended use of the claimed method for rational discovery
of antisense oligonucleotides and is given no patentable weight. Thus, the specification
need only enable a method for rational discovery of antisense oligonucleotides which
target transcriptional regulators, consistent with the claimed method steps.
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Appellant argues the specification provides four working examples of the
instantly claimed methods.1 Brief, pages 10-11. Appellant argues the
“Examiner's contention that the antisense molecule OL-1 p53 is ineffective at
down regulating p53 expression and controlling the aberrant growth of cancer
cells is contradicted by the data presented in the instant application.” Brief, page
16. Appellants particularly argue (Brief, pages 16-18) that
Bayever et al. (1994) found that five different p53 antisense
oligonucleotides had the same effect on AML blasts which was not
observed with control, non-specific oligonucleotides. Figure 2 of the
present specification demonstrates that OL(l)p53 inhibits the growth of
acute myelogenous leukemia blasts in culture. Bayever et al. Antisense
Research and Development 3:383-390 (1993) report that following
administration of OL(l)p53 to patients, bone marrow samples obtained
therefrom showed lower cumulative cell production in long term cultures ...
implying that the infusion of the oligonucleotide may have inhibited
leukemic cell growth. … Notably, Bishop et al. suggest that the efficacy of
the OL(l)p53 may be enhanced via combination with currently available
chemotherapeutics, e.g., an augmentation agent as disclosed in the
instant specification. … Moreover, both Bishop et al. and Yuen et al.
indicate that OL(l)p53 has promise for use in combination with a DNA
damaging agent, e.g., an augmentation agent. Thus, contrary to the
Examiner's assertion, none of the three references refutes the potential
usefulness of OL(l)p53 in treating cancer.

1 Example 1 describes in vitro comparisons of four antisense
oligonucleotides which hybridize to the p53 gene. Activity was determined
as a function of reduction in viable cell counts and the inability of treated
cells to grow as colonies in colony forming assays. Example 2 describes
the results obtained using antisense oligonucleotides and variants thereof
specific for the MDRl gene following treatment of human multiple myeloma
cells with the same. Example 3 describes the results obtained when the
A427 human lung cancer cell line is contacted with antisense
oligonucleotides and variants thereof which target the MRP gene.
Antisense oligonucleotides which hybridize to the Jun-D gene are
evaluated in Example 4.
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Each of the examples cited by appellant, and as provided in the
specification, would reasonably appear to support appellant’s position that the
antisense molecule OL-1 p53 is effective at down-regulating p53 expression and
controlling the aberrant growth of cancer cells, albeit in vitro. Thus appellant’s
evidence shows the potential of the antisense molecule OL-1 p53 sequence to
target a transcriptional regulator. This is all that is required by claim 7. Any
potentially useful antisense oligonucleotide discovered by the claimed rational
discovery method can later be tested for its potential use as a therapeutic.
However, an actual usefulness of discovered antisense oligonucleotides as a
therapeutic, in our view, is not a requirement of the claimed rational discovery
method.
Enablement is a legal determination of whether a patent enables one
skilled in the art to make and use the claimed invention, Raytheon Co. v. Roper
Corp., 724 F.2d 951, 960, 220 USPQ 592, 599 (Fed. Cir. 1983), and is not
precluded even if some experimentation is necessary, although the amount of
experimentation needed must not be unduly extensive, Atlas Powder Co. v. E.I.
Du Pont De Nemours & Co., 750 F.2d 1569, 1576, 224 USPQ 409, 413 (Fed.
Cir. 1984).
In agreement with appellant, we find the specification provides at least four
working examples of the claimed method of discovering antisense oligonucleotides
which target transcriptional regulators. The examiner has not explained why one of
ordinary skill in the art practicing the claimed method steps would require undue
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experimentation. Since the claimed method does not require the tested
oligonucleotides to be therapeutically effective, and the specification provides at least
four working examples of the discovery of antisense oligonucleotides consistent with the
claimed method steps, we conclude that the specification enables the claimed method
for rational discovery of antisense oligonucleotides which target transcriptional
regulators.
In sum, the examiner has not explained why one of ordinary skill in the art
practicing the claimed method steps would require undue experimentation. Therefore,
the rejection of claims 7, 8, 41, 45, 46, 48, 53, 74, 88, 91, 92 and 96-100 under 35
U.S.C. §112, first paragraph for failing to comply with the enablement requirement is
reversed.
REVERSED

)
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. 2006-0865
Application No. 08/472,801

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