Ex parte Gleave

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for publication and is not binding precedent of the Board.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 pane MARTIN GLEAVE and HlDEAKl M 	I 	Y 	Y 	I
Appeal No. 2005-2447
Application No. 09/619,908
JAN 3 1 2006 	1
HEARD: October 18, 2005
U.S. pATENT AND TAADEMARK OFFICE
Before SCHEINER, ADAMS and MILLS, Administrative Patent Judues.
SCHEINER, Administrative Patent Judae.
DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. $j134 from the final rejection of
claims 1-23 and 26-40. Claims 24 and 25, also pending in the application, have been
allowed.
BACKGROUND
Insulin-like growth factor (IGF)-I and IGF-II are potent mitogens for many
normal and malignant cells. Accumulating evidence suggests that lGFs
play an important role in the pathophysiology of prostatic disease and
breast cancer. . . .
The biological response to [IGFs] is regulated by various factors, including
IGFBPs [(insulin-like growth factor binding proteins)]. To date, six IGFBPs
have been identified whose function is believed to involve modulation of
the biological actions of the lGFs through high affinity interactions . . .
However, some evidence suggests biological activity for IGFBPs that are
independent of IGFs, . . . and both stirnulatory and inhibitory effects of
IGFBPs on cell proliferation have been reported under various
experimental conditions. . . .
Specification, pages 1-2.

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"[Plrostate cancer is an androgen-sensitive tumor, [thus,] androgen
withdrawal . . . is utilized in some therapeutic regimens . . . [and] leads to
extensive apoptosis in the prostate tumor, and hence to a regression of the
disease. However, . . . apoptosis is not complete, and a progression of surviving
tumor cells to androgen-independence ultimately occurs." I	d	.	, 	page 1. The
present invention is concerned with delaying the ultimate progression of tumor
cells to androgen-independence.
Appellants "initially characterized the changes [in] IGFBPs expression in
the Shionogi tumor model' after castration and during [progression to androgen-
independence]" (Specification, page 5). "Of the IGBFPs expressed in Shionogi
tumors, the most dramatic changes in expression were observed with IGFBP-5.
Despite undetectable levels in [androgen-dependent] intact tumors, IGFBP-5
expression is highly upregulated after castration, and remains highly expressed
in [androgen-independent] tumors." Id.,pages 5-6. Moreover, "[tlhe pattern of
' "The Shionogi tumor model is a xenograft of an androgen-dependent mouse
mammary carcinoma that grows subcutaneously in male syngenic hosts."
Specification, pages 4-5. 	Shionogi tumor cells "are highly tumorigenic and locally
invasive . . . [and] have been shown to respond to androgen withdrawal in a manner
which mimics the observed behavior of prostatic tumor cells," that is, "androgen
withdrawal precipitates apoptosis and tumor regression in a highly reproducible
manner" (id.,page 5). "Further, changes in expression of peptides . . . in human
prostate cancer following castration and during progression to androgen-independence
are similar to those observed in Shionogi tumor cells. Because of these similarities, the
Shionogi tumor model mimics human prostate cancer and provides a very useful model
for the evaluation of the ability of compounds to delay the onset of androgen-
independence. Despite complete tumor regression after castration, rapidly growing
androgen-independent Shionogi tumors invariably recur after one month, which
provides a reliable end point to evaluate agents which can delay the progression to
androgen-independence." Id.

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Application No. 09/619,908
IGFBP-5 upregulation in the Shionogi tumor model during [progression to
androgen-independence] . . . is similar to that in rat prostate . . . and human
prostate" (id.,page 6).
According to appellants, antisense oligodeoxynucleotides (ODNs)
complementary to portions of the gene encoding IGFBP-5 "inhibit[ ] cell
proliferation and induce[ ] cell cycle arrest in Shionogi tumor cells in a time- and
dose-dependent manner. . . [and do] not appear to induce apoptosis either jr~
vitro or in vivo 	. . suggest[ing] that antisense IGFBP-5 activity occurs via	- 	1 	.
inhibition of cell proliferation rather than induction of apoptosis." Id. Appellants
"hypothesized that targeting upregulation precipitated by androgen using [an]
antisense strategy might inhibit progression to androgen-independence." I	d	.	,
page 7. In appellants' "in vivo experiments, administration of antisense IGFBP-5
after castration delayed time to [androgen-independence] . . . and inhibited
[androgen-independent] recurrent tumor growth." Id.
THE CLAIMS
The present invention is directed to "a method for delaying the' progression of
hormone-regulated (prostatic or breast) tumor cells to hormone (e.g. androgen or
estrogen) independence, a therapeutic method for the treatment of individuals . . .
suffering from hormone regulated cancers, such as breast or prostate cancer, and
therapeutic agents effective for use in such methods." Specification, page 4. In
addition, the present invention is directed to a method of inhibiting or delaying
metastatic boney progression of an IGF-1 sensitive tumor in a mammal. We note that
the claims on appeal require an antisense oligonucleotide that inhibits expression of

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Application No. 09/61 9,908
Page 4
IGFBP-5, with the exception of method claims 8, 12, 15, 19, 39 and 40, which merely
require "a composition effective to inhibit expression of IGFBP-5."
Claims 1, 8, 15 and 22 are representative of the subject matter on appeal:
1. A method for delaying progression of hormone-regulated mammalian tumor
cells to an androgen-independent state, comprising treating hormone-sensitive
mammalian tumor cells with an antisense oligonucleotide which inhibits expression of
IGFBP-5 by the tumor cells.
8. A method for treating a hormone-responsive cancer in a mammalian
individual suffering from hormone-responsive cancer, comprising the steps of initiating
hormone-withdrawal to induce apoptotic cell death of hormone-responsive cancer cells
in the individual, and administering to the individual a composition effective to inhibit
expression of IGFBP-5 by the hormone-responsive cancer cells, thereby delaying the
progression of hormone-responsive cancer cells to a hormone-independent state in the
individual.
15. A method for inhibiting or delaying metastatic boney progression of an IGF-1
sensitive tumor in a mammal, comprising the step of administering to the mammal a
composition effective to inhibit expression of IGFBP-5 by the hormone-responsive
cancer cells, thereby inhibiting or delaying metastatic boney progression of the tumor.
22. A composition for treatment of hormone-regulated cancer comprising an
antisense oligonucleotide which inhibits expression of IGFBP-5 by hormone-regulated
tumor cells.
THE REJECTIONS
The claims stand rejected as follows:
I. Claims 1, 5, 22 and 36-38* under 35 U.S.C. 5 102 (b) as anticipated by
H ~ y n h . ~
Claims 36-38 were subject to this ground of rejection in the final rejection
(paper no. 14, January 24, 2003)) but were omitted from the examiner's statement of
the rejection in the Answer. The omission of these claims appears to have been a
typographical error, as they are specifically discussed in the examiner's response to
appellants' arguments (see, e.g., page 16 of the Answer).
Huynh et al., "A Role for Insulin-like Growth Factor Binding Protein 5 in the
Antiproliferative Action of the Antiestrogen ICI 182780," Cell Growth & Differentiation,
Vol. 7, pp. 1501-1506 (November 1996)

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Application No. 09/619,908
Page 5
II. Claims 1-3, 5, 6, 22, 23, 26-28, and 36-384under 35 U.S.C. 5 103 (a) as
unpatentable over Huynh in view of Kiefer15Baracchini6and Nickerson.'
Ill. Claims 1-3, 4, 6 , 8-10, 12, 13, 15-17, 19, 20, 22, 23 and 38-40 under the first
paragraph of 35 U.S.C. 5 112, written description.
IV. Claims 1-23 and 26-40 under the first paragraph of 35 U.S.C. 9 112,
enablement.
DISCUSSION
I. Anticipation
Claims 1, 5, 22 and 36-38 stand rejected under 35 U.S.C. 5 102 (b) as
anticipated by Huynh. Claims 1, 5 and 38 are method claims, while claims 22, 36 and
,37 are composition claims. Appellants argue that the method and composition claims
do not stand or fall together because "anticipation of a method claim requires a different
content of the reference than a composition claim, which need only disclose the same
composition, rather than the same method steps." Brief, page 3. Accordingly, we will
consider claim 1 to be representative of the method claims, and claim 22 to be
representative of the composition claims - claims 5 and 38 will stand or fall with claim 1,
while claims 36 and 37 will stand or fall with claim 22.
Claim 1 is directed to a method of delaying progression of hormone-regulated
Claim 40 was included in this rejection in the final rejection, but the rejection
was withdrawn with respect to claim 40 in the Examiner's Answer (page 17).
Kiefer et al., "Molecular Cloning of a New Human Insulin-like Growth Factor
Binding Protein," Biochem. Bio~hvs.Res. Commun., Vol. 176, No. 1, pp. 219-225
(1991).
U.S. Patent No. 5,801,154, issued to Baracchini et al. on September 1, 1998.
Nickerson et al., "Castration-Induced Apoptosis in the Rat Ventral Prostate is
Associated with Increased Expression of Genes Encoding Insulin-Like Growth Factor
Binding Proteins 2, 3, 4 and 5," Endocrinolo~v,Vol. 139, No. 2, pp. 807-810 (1998).

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Application No. 09/61 9,908
mammalian tumor cells to an androgen-independent state by treating the cells with an
antisense oligonucleotide which inhibits expression of IGFBP-5 by the tumor cells.
According to the examiner, "a key limitation is that the method steps are carried out in
hormone sensitive mammalian tumor cells" (Answer, page 14), and "Huynh discloses
administering+anantisense oligomer comprising 21 nucleotides targeted to IGFBP-5 to
breast cancer cells" (	i	d	.	, 	page 5). The examiner acknowledges that Huynh says nothing
about delaying progression of hormone-regulated mammalian tumor cells to an
androgen-independent state, but argues that "any recited outcome such as that is
merely considered to be an inherent feature, since all the structural and manipulative
features of the claim are present in Huynh" (id.).
It is well settled that a prior art reference may anticipate even when claim
limitations are not expressly found in that reference, but are nonetheless inherent in it.
See, e.g., Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 51 USPQ2d 1943 (Fed. Cir.	-
1999); Titanium Metals C o r ~ .v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985).
However, it is also the case that "[ilnherency . . . may not be established by probabilities
or possibilities. The mere fact that a certain thing mav result from a given set of
circumstances is not sufficient." 	In re Oelrich, 666 F.2d 578, 581, 212 USPQ 323, 326
(CCPA 1981).
Here, Huynh teaches that "IGFBP-5 can either stimulate or inhibit cellular
proliferation in different experimental systems . . . suggest[ing] that there are poorly
characterized complexities in IGFBP-5 action" (Huynh, pages 1503-1504). Indeed, on
this record, there is no dispute that "Huynh [ I actually teach[es] that antisense to
IGFBP-5 stimulates cell proliferation in the [MCF-71 breast cancer cell line used"
(Answer, page 14), while it inhibits proliferation in the Shionogi tumor cells used by

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Page 7
appellants. According to the examiner, this variation in the effects of antisense IGFBP-
5 is irrelevant "because cellular proliferation (or inhibition thereof) is not recited as a
claim limitation" (	i	d	.	)	. 	In our view, however, this variation 	relevant because it shows
that in the only directly comparable parameter of record, the two cell lines react
differently to inhibition of IGFBP-5. While Huynh says nothing about delayed
progression to androgen-independence, it is not unreasonable to expect that the two
cell lines might react differently to inhibition of IGFBP-5 in this respect as well,
especially in light of Huynh's suggestion that the actions of IGFBP-5 are poorly
characterized. In our view, the examiner has established that inhibition of IGFBP-5 in
Huynh's MCF-7 cells miaht delay progression to androgen-independence, but has not
established that it a.	As discussed above, this is not sufficient to establish a prima
facie case of anticipation based on inherency.
Accordingly, the rejection of claims 1, 5 %nd 38 as anticipated by Huynh is
reversed.
Claim 22, however, stands on a different footing. Claim 22 is directed to "a
composition for treatment of hormone-regulated cancer comprising an antisense
oligonucleotide which inhibits expression of IGFBP-5 by hormone-regulated tumor
cells." Huynh plainly describes an IGFBP-5 antisense oligodeoxynucleotide which
reduces expression of IGFBP-5 in human breast cancer cells. Appellants argue that
"the phrase 'for treatment of hormone-regulated cancer' is more than a statement of
intended use and deserves to be given weight in assessing the scope of the claims."
Brief, page 7. According to appellants, "Huhnh's antisense is not used in the treatment
of any animal or human . . . [thus,] [tlhere is no teaching of a composition suitable for

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Application No. 09/61 9,908
administration in the treatment of cancer." Id. Nevertheless, appellants have not
pointed out anything which makes Huynh's IGFBP-5 antisense oligonucleotide
composition unsuitable for administration to an animal, or which distinguishes it from
the claimed IGFBP-5 antisense oligonucleotide composition in any way.
Accordingly, the rejection of claim 1 as anticipated by Huynh is affirmed. As
discussed above, claims 36 and 37 stand or fall with claim 22, thus the rejection of
claims 36 and 36 as anticipated by Huynh is affirmed as well.
II. Obviousness
Claims 1-3, 5, 6, 22, 23, 26-28, and 36-38 stand rejected under 35 U.S.C. § 103
(a) as unpatentable over Huynh in view of Kiefer, Baracchini and Nickerson. Having
already determined that Huynh anticipates the subject matter of claims 22, 36 and 37,
we affirm the rejection under 35 U.S.C. $j103 (a) with respect to those claims.
"[Alnticipation is the epitome of obviousness." Connell v. Sears, Roebuck & Co., 722
F.2d 1542, 1548, 220 USPQ 193, 198 (Fed. Cir. 1983).
Claims 1-3, 5, 6, 23, 26-28 and 38, on the other hand, are directed to methods of
delaying the progression of hormone-regulated tumor cells to an androgen-independent
state; to treating a hormone-responsive cancer; and to delaying metastatic boney
progression of IGF-1 sensitive tumors by inhibiting IGFBP-5.
The examiner relies on Huynh for disclosure of "an antisense oligomer
comprising 21 nucleotides targeted to IGFBP-5 that was administered to breast cancer
cells" (Answer, page 6); on Kiefer for disclosure of the translation initiation and
termination regions of IGFBP-5 (id.);and on Baracchini for "teach[ing] that the
translation initiation and termination regions are preferred regions for targeting with

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Application No. 09/61 9,908
antisense oligos" (id.). According to the examiner, these references provide motivation
for targeting particular regions of IGFBP-5 in order to inhibit its effects. Id.,pages 6-7.
Nevertheless, in our view, the dispositive issue here is the examiner's proposed
rationale for inhibiting IGFBP-5 in tumor cells in the first place. The underlying premise
of the examiner's rejection is that "Nickerson teaches that prostatic tumor cells over-
express IGFBP-5 and [that IGFBP-51is involved in tumorigenesis" (&, 	page 6), and
that, therefore, it would have been obvious for one skilled in the art to inhibit IGFBP-5
expression in prostatic tumor cells (id.,page 7).
We see no factual basis for the examiner's expansive interpretation of
Nickerson's teachings. 	Nickerson's experiments were designed "to study the gene
expression of IGFBPs during involution of the rat ventral prostate after castration."
Nickerson, page 807. The experiments demonstrated that "IGFBP-5 mRNA increases
in the ventral prostate 2-fold by 24 h and 5-fold by 72 h [ I in keeping with the
hypothesis that IGFBP-5 may be involved in apoptosis resulting from steroid hormone
deprivation." Id.,page 809, left-hand column. According to Nickerson, the
experimental system could not determine "whether IGFBPs cause apoptosis in the
ventral prostate or are upregulated as a result of apoptosis." I	d	.	, 	right-hand column.
Either way, the examiner has not explained how Nickerson's observations suggest that
IGFBP-5 is involved in tumorigenesis, or why one skilled in the art would have wanted
to inhibit its effects.
The examiner bears the initial burden of establishing prima facie obviousness.
See In re Riickaert, 9 F.3d 1531, 1532, 28 USPQ2d 1955, 1956 (Fed. Cir. 1993). To
support a prima facie conclusion of obviousness, the prior art must disclose or suggest
all the limitations of the claimed invention. See In re Lowry, 32 F.3d 1579, 1582, 32

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Page 10
USPQ2d 1031 , 1034 (Fed. Cir. 1994). In addition, the record must provide evidence
that those of skill in the art would have had a reasonable expectation of success in
doing so. See In re Dow Chemical Co., 837 F.2d 469,473,5 USPQ2d 1529, 1531
(Fed. Cir. 1988).
We agree with appellants that the examiner's rejection "fails to state a prima
facie case of obviousness." Brief, page 8. The rejection of claims 1-3, 5, 6, 23, 26-28
and 38 under 35 U.S.C. 3 103 is reversed.
Ill. Written Description
Claims 1-3, 4, 6, 8-10, 12, 13, 15-17, 19, 20, 22, 23 and 38-40 stand rejected
under the first paragraph of 35 U.S.C. 3 112, as lacking adequate written descriptive
support.
"The 'written description' requirement serves a teaching function, . . . in which the
public is given 'meaningful disclosure in exchange for being excluded from practicing
the invention for a limited period of time."' 	Universitv of Rochester v. G.D. Searle & Co.,
Inc 	358 F.3d 916, 922, 69 USPQ2d 1886, 1891 (Fed. Cir. 2004) (citation omitted).	1
Another "purpose of the 'written description' requirement is . . . [to] convey with
reasonable clarity to those skilled in the art that, as of the filing date [ I , [the applicant]
was in possession of the invention." Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563-
64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991). See also Enzo Biochem Inc. v. Gen-
Probe Inc., 296 F.3d 1316, 1329, 63 USPQ2d 1609, 1617 (Fed. Cir. 2002). The
requirement is satisfied when the specification "set[s] forth enough detail to allow a
person of ordinary skill in the art to understand what is claimed and to recognize that
the inventor invented what is claimed." Universitv of Rochester, 358 F.3d at 928, 69

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USPQ2d at 1896. Whether or not a specification satisfies the requirement is a question
of fact, which must be resolved on a case-by-case basis (Vas-Cath, 935 F.2d at 1562-
63, 19 USPQ2d at 1116), and it is the examiner's "initial burden [to] present[ ] evidence
or reasons why persons skilled in the art would not recognize in the disclosure a
description of the invention defined by the claims" (In re Wertheim, 541 F.2d 257, 263,
191 USPQ 90,97 (CCPA 1976)).
With respect to claims 1-3, 4, 6, 9, 10, 13, 16, 17, 20, 22, 23 and 38, we
disagree with the examiner's rationale and conclusion. These claims require antisense
oligonucleotides, of varying scope, which inhibit expression of IGFBP-5 in hormone-
regulated mammalian tumor cells. The examiner argues that "[tlhe specification . . .
only describes two target IGFBP-5 sequences, [mouse and human] . . . , and does not
describe any additional sequences that can be targeted via antisense oligos. Without
such a description, the skilled artisan would not be able to envision any other target
sequences and thus would not be able to synthesize an antisense oligo specific for the
sequence" (Answer, page 8), and moreover, would be "required to undertake de novo
experimentation to isolate and identify IGFBP-5 encoding nucleic acids" (id.).
Nevertheless, "applicants have some flexibility in the 'mode selected for
compliance' with the written description requirement" (Universitv of Rochester, 358 F.3d
at 928, 69 USPQ2d at 1896), and it is well settled that actual reduction to practice is not
necessary to satisfy the requirement (id.at 926, 69 USPQ2d at 1894). On the other
hand, "[iln claims to genetic material . . . [a] definition by function . . . does not suffice to
to define [a] genus because it is only an indication of what the [material] does, rather
than what it is." Universitv of California v. Eli Lillv and Co., 119 F.3d 1559, 1568, 43
USPQ2d 1398, 1406 (Fed. Cir. 1997). The court explained that "[aln adequate written

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Page 12
description of a DNA . . . 'requires a precise definition, such as by structure, formula,
chemical name, or physical properties,"' (id.at 1566, 43 USPQ2d at 1404) while "[a]
description of a genus of cDNAs may be achieved by means of a recitation of a
representative number of cDNAs, defined by nucleotide sequence, falling within the
scope of the genus or of a recitation of structural features common to the members of
the genus, which features constitute a substantial portion of the genus1'(id.at 1568, 43
USPQ2d at 1406). Subsequently, the court clarified that "the written description
requirement would be met for [a claim] . . . if [a] functional characteristic . . . were
coupled with a disclosed correlation between that function and a structure that is
sufficiently known or disclosed." Enzo Biochem, 296 F.3d at 1324-25, 63 USPQ2d at
1613.
Here, the specification sets forth the sequences of DNA molecules encoding the
mouse and human IGFBP-5s, as well as a number of antisense sequences targeting
specific regions of the mouse and human IGFBP-5 DNAs. The examiner's rationale
would seem to limit the claimed genus to only those antisense oligonucleotides
explicitly recited, without explaining why one skilled in the art would not have expected
the mouse and human DNAs to be representative of, or have considerable structural
similarity to, DNA encoding IGFBP-5 in other mammals. Again, it is the examiner's
"initial burden [to] present[] evidence or reasons why persons skilled in the art would
not recognize in the disclosure a description of the invention defined by the claims"
(Wertheim, 541 F.2d at 263, 191 USPQ at 97). We find that the examiner has not done
SO.
Accordingly, the rejection of claims 1-3, 4, 6, 9, 10, 13, 16, 17, 20, 22, 23 and 38
as lacking adequate written descriptive support under 35 U.S.C. § 112, first paragraph,
is reversed.

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Page 13
With respect to claims 8, 12, 15, 19, 39 and 40, however, we agree with the
examiner that adequate written descriptive support is lacking. We note that these
claims merely require "a composition" effective to inhibit expression of IGFBP-5. The
only such compositions disclosed in the specification are the afore mentioned antisense
oligonucleotides. The examiner's position is essentially that the specification does not
provide "any description, structural[ ] or otherwise, of IGFBP-5 inhibitors other than the
instantly described antisense oligo[nucleotides]" and that the instantly described
antisense oligonucleotides are "not representative of the breadth of inhibitors sought in
the instant claims" (Answer, page 8).
Appellants argue that "the invention is based on the discovery . . . that reducing
the expression of IGFBP-5 in hormone-responsive cancer cells has therapeutic
benefits" (Brief, page 12), and "antisense inhibitors of IGFBP-5 expression [are]
examples of a methodology that can be used in practicing the methods" (	i	d	.	, 	page 13).
Appellants argue that the invention "is not antisense technology per se. 	It is also not
the identification of IGFBP-5, nor any and all inhibitors of IGFBP-5 expression" (id.,
page 12).
These arguments are not persuasive. The Federal Circuit has recently held that
the written description standard discussed in Eli Lillv applies to methods as well as
products. 	Universitv of Rochester v. G.D. Searle & Co.. Inc., 358 F.3d 916, 926, 69
USPQ2d 1886, 1894 (Fed. Cir. 2004): "Regardless whether a compound is claimed per
se or a method is claimed that entails the use of the compound, the inventor cannot lay
claim to that subject matter unless he can provide a description of the compound
sufficient to distinguish infringing compounds from non-infringing compounds, or
infringing methods from non-infringing methods."

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Page 14
The facts in Rochester are similar to those of the instant application. Rochester
involved a "method for selectively inhibiting PGHS-2 activity in a human host,
comprising administering a non-steroidal compound that selectivelv inhibits activitv of
the PGHS-2 aene product to a human host in need of such treatment." Id.at 920, 69
USPQ2d at 1888 (emphasis added). The court noted that the relevant patent described
the cells needed to screen for compounds having the recited property, as well as
"assays for screening compounds, including peptides, polynucleotides, and small
organic molecules to identify those that inhibit the expression or activity of the PGHS-2
gene product." Id.At 927, 69 USPQ2d at 1895. Nevertheless, the court concluded that
the patent's disclosure was inadequate to enable the claimed method because the
patent "[did] not disclose just which peptides, polynucleotides, and small organic
molecules have the desired characteristic of selectively inhibiting PGHS-2." Id.
(emphasis in original, internal quotations omitted). "Without such disclosure, the
claimed methods cannot be said to have been described." Id.
In this case, as in Rochester, the claims are directed to a process for
accomplishing a desired result (in Rochester, selectively inhibiting PGHS-2 activity in a
human host; here, "inhibiting expression of IGFBP-5 in hormone-responsive cells")
using a composition having a specified functional property (in Rochester, a "non-
steroidal compound that selectively inhibits activity of the PGHS-2 gene product"; here,
"a composition effective to inhibit expression of IGFBP-5"). And in this case, as in
Rochester, the specification provides no description whatsoever of just which
compositions have the functional property recited in the claims - the genus recited in
the claims is defined exclusively in functional terms, i.e., in terms of what the members
of the genus do, rather than what they are.

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Application No. 09/61 9,908
As discussed above, "[a] definition by function . . . does not suffice to define [a]
genus because it is only an indication of what the [material] does, rather than what it is."
Eli Lillv, 119 F.3d at 1568, 43 USPQ2d at 1406. To paraphrase Eli Lillv, naming a type
of material, which may or may not exist, in the absence of knowledge as to what that
material consists of, is not a description of that material. See id. Accordingly, the
rejection of claims 8, 12, 15, 19, 39 and 40 as lacking adequate written descriptive
support under 35 U.S.C. 5 112, first paragraph, is affirmed.
IV. Enablement
Claims 1-23 and 26-40, all the claims on appeal, stand rejected under 35 U.S.C.
$1 12, first paragraph, as lacking enablement. According to the examiner, the claims
are drawn to "antisense oligo[nucleotides] targeted to any transcript of IGFBP-5 as well
as methods of treatment using said antisense oligo[nucleotides]" (Answer, page 9), but
the specification "is only enabling for antisense oligos of SEQ ID NO:1 targeted to the
IGFBP-5 transcripts of [murine] SEQ ID NO:13, and for the use of SEQ ID NOS; 2, 3
and 9 in the inhibition of SEQ ID NO:14 in vitro, and does not provide guidance on the
in vivo inhibition of [human] SEQ ID NO:14" (id.).	--
With respect to claims 1-7, 9-1 1, 13, 14, 16-18, 20-23 and 26-48, all of which
require an antisense oligonucleotide capable of inhibiting expression of IGFBP-5, we do
not agree with the examiner's rationale or conclusion, for the reasons that follow.
Initially, however, we note that the examiner has focused exclusively on the therapeutic
use of antisense oligonucleotides, and has not separately addressed the enablement of
those claims that do not require antisense oligonucleotides (as was done in the written
description rejection above). Nevertheless, our affirmance of the written description
rejection for claims 8, 12, 15, 19, 39 and 40 constitutes a disposition of these broader

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Application No. 09/619,908
claims, so we need not reach the merits of the enablement rejection with respect to
these claims.
Returning to claims 1-7, 9-1 1, 13, 14, 16-18, 20-23 and 26-48, then, we find that
the reasons cited in support of the examiner's rejection are insufficient to support the
examiner's conclusion that these claims are not enabled by the specification.
"The first paragraph of 35 U.S.C. 5 112 requires, inter alia, that the specification
of a patent enable any person skilled in the art to which it pertains to make and use the
claimed invention. Although the statute does not say so, enablement requires that the
specification teach those in the art to make and use the invention without 'undue
experimentation.' In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir.
1988).[*] That some experimentation may be required is not fatal; the issue is whether
the amount of experimentation is 'undue."' In re Vaeck, 947 F.2d 488, 495, 20 USPQ2d
1438, 1444 (Fed. Cir. 1991) (emphasis in original). Nevertheless, "[wlhen rejecting a
claim under the enablement requirement of section 112," it is well settled that "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,
Factors to be considered in determining whether a disclosure would
require undue experimentation have been summarized by the
board in Ex parte Forman [230 USPQ 546,547 (BdPatApplnt
1986)l. They include (1) the quantity of experimentation
necessary, (2) the amount of direction or guidance presented,
(3) the presence or absence of working examples, (4) the nature of
the invention, (5) the state of the prior art, (6) the relative skill of
those in the art, (7) the predictability or unpredictability of the art,
and (8) the breadth of the claims (footnote omitted).
In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).

Appeal No. 2005-2447
Application No. 09/61 9,908
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of course, providing sufficient reasons for doubting any assertions in the specification
as to the scope of enablement." 	In re Wriaht, 999 F.2d 1557, 1561, 27 USPQ2d 1510,
1513 (Fed. Cir. 1993).
According to the examiner, "the clinical application of antisense therapy is a
highly unpredictable art due to obstacles that still face antisense therapy" (Answer,
page 9). The obstacles enumerated by the examiner are essentially: the identification
of an appropriate target in the disease process; the identification of a molecule that can
interfere with the disease process through specific recognition and affinity; the
complexity of cellular uptake of oligonucleotides; and physical barriers due to internal
structures of target RNAs and associations with cellular proteins. Id.,pages 9-10. In
addition, the examiner relies on Gewirtzgand Branch'' as evidence that "'the antisense
approach has generated controversy [among those of skill in the art] with regard to
mechanism of action, reliability, and ultimate therapeutic utility"' (	i	d	.	, 	page 1O), and the
sense in the art is that "'efforts should be increased . . . to learn how they may be used
successfully in the clinic"' (id.).
We have no reason to doubt the examiner's assessment of the state of the art in
general, and we think it is fair to say that the field of antisense therapy is indeed
recognized as highly unpredictable by those of skill in the art. Nevertheless, appellants
point out, and the examiner appears to acknowledge, that appellants have identified the
murine and human IGFBP-5s as appropriate targets in treating androgen-dependent
cancers like prostate cancer and breast cancer, and that appellants have identified
Giwirtz et al., "Facilitating Oligonucleotide Delivery: Helping Antisense Deliver
on Its Promise," Proc. Natl. Acad. Sci. USA, Vol. 93, pp. 3161-3163 (April, 1996).
l o Branch, A.D., "A Good Antisense Molecule is Hard to Find," TIBS, Vol. 23, pp.
50 (February, 1998).

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Application No. 09/61 9,908
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antisense IGFBP-5 molecules that can delay progression to androgen independence in
the Shionogi tumor model (asserted to be a useful model of human prostate cancer)
and/or inhibit expression of IGFBP-5 in human prostate cancer cell lines. See page 17
of the substitute Brief for Appellant (submitted June 10, 2004), and page 9 of the
Answer. This concrete guidance, in the form of working examples, would seem to
address a number of the examiner's specific concerns, and weigh in favor of finding the
specification enabling for claims directed to antisense inhibition of IGFBP-5. In any
case, the examiner has not explained why the specific guidance in the specification
would not, at least to some extent, mitigate or counterbalance any remaining factors
(e.g., the generally unpredictable nature of the field) tending to weigh against a finding
of enablement. In other words, the examiner has not explained why identifying other
antisense IGFBP-5 molecules capable of delaying progression of hormone-regulated
tumor cells to androgen-independence, either in vivo or in vitro would have required
undue experimentation, given the specific guidance provided by appellants in their
working examples.
Accordingly, the rejection of claims 	1-7, 9-11, 13, 14, 16-18, 20-23 and 26-48
as lacking enablement under the first paragraph of 35 U.S.C. § 112 is reversed.
SUMMARY
I. The rejection of the claims under 35 U.S.C. § 102 (b) as anticipated by Huynh
is affirmed with respect to claims 22, 36 and 37, and reversed with respect to claims 1,
5 and 38.
II. The rejection of the claims under 35 U.S.C. § 103 (a) as unpatentable over
Huynh, Kiefer, Baracchini and Nickerson is affirmed with respect to claims 22, 36 and
37, and reversed with respect to claims 1-3, 5, 6, 23, 26-28 and 38.

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Application No. 09/619,908
Page 19
Ill. The rejection of the claims under 35 U.S.C. 9 112, first paragraph, as lacking
adequate written descriptive support is affirmed with respect to claims 8, 12, 15, 19, 39
and 40, and reversed with respect to claims 1-3, 4, 6, 9, 10, 13, 16, 17, 20, 22, 23 and
38.
IV. The rejection of the claims under 35 U.S.C. 5 112, first paragraph, as lacking
enablement is reversed with respect to claims 1-7, 9-11, 13, 14, 16-18, 20-23 and 26-
48. We do not reach the merits of this rejection with respect to claims 8, 12, 15, 19, 39
and 40.
TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with this appeal
may be extended under 37 CFR 5 1.I	36 (a).
AFFIRMED-IN-PART
- Toni R. Scheiner
Administrative Patent Judge
1
1
) BOARD OF PATENT
)
Donald E. Adams 	) APPEALS AND
Administrative Patent Judge 	1
) INTERFERENCES
1
)
)

Appeal No. 2005-2447
Application No. 09/619,908
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