Ex Parte Schwinn

Board of Patent Appeals and Interferences

Aug 6, 2009

10268969 (B.P.A.I. Aug. 6, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte DEBRA A. SCHWINN
__________

Appeal 2009-004912
Application 10/268,969
Technology Center 1600
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Decided: August 7, 2009
__________

Before DEMETRA J. MILLS, RICHARD M. LEBOVITZ, and
STEPHEN WALSH, Administrative Patent Judges.

WALSH, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
method of treating bladder symptoms. The Patent Examiner rejected the
claims for lacking descriptive and enabling support. We have jurisdiction
under 35 U.S.C. § 6(b). We affirm-in-part.
Appeal 2009-004912
Application 10/268,969

STATEMENT OF THE CASE
According to the Specification, the invention “is based on the
recognition of α1d[-adrenergic receptor or AR] as the α1AR subtype
responsible for irritative symptoms associated with bladder and lower
urinary tract diseases.” (Spec. 6:12-14.) “The method of treatment to which
the invention relates comprises administering to a patient suffering irritative
symptoms an amount of an α1dAR antagonist sufficient to relieve such
symptoms.” (Id. at 18-20.) Claims 1-10, which are all the pending claims,
are on appeal. Claims 1 and 9 are representative and read as follows:
1. A method of treating irritative symptoms of bladder or lower urinary
tract disease comprising administering to a patient in need of such
treatment an amount of an α1d-adrenergic receptor (α1dAR) antagonist
sufficient to effect said treatment.

9. A method of treating irritative symptoms of bladder or lower urinary
tract disease comprising administering to a patient in need of such
treatment an effective amount of a construct comprising an
oligonucleotide that inhibits production of α1dAR or that encodes a
molecule that inhibits production of α1dAR.

The Examiner relied on the following evidence:
Dwaine A. Braasch et al., Novel Antisense and Peptiode Nucleic Acid
Strategies for Controlling Gene Expression, 41 BIOCHEM. 4503-10 (2002).

Alan M. Gewirtz et al., Facilitating oligonucleotide delivery: Helping
antisense deliver on its promise, 93 PROC. NATL. ACAD. SCI. USA 3161-63
(1996).

Sudhir Agrawal, Antisense oligonucleotides: towards clinical trials,
14 TIBTECH 376-87 (1996).

Andrea D. Branch, A good antisense molecule is hard to find, 23 TIBS 45-
50 (1998).

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Ingo Tamm et al., Antisense therapy in oncology: new hope for an old idea?,
358 THE LANCET 489-97 (2001).

The Examiner rejected the claims as follows:
• claims 1-8 under 35 U.S.C. § 112, ¶ 1, for lack of compliance with
the written description requirement, i.e., for failure to provide descriptive
support for the scope of the genus “antagonist” used in the claimed method;
and
• claims 1-10 under 35 U.S.C. § 112, ¶ 1, for lack of compliance with
the enablement requirement, i.e., for failure to enable in vivo treatment with
inhibitor oligonucleotide constructs.

WRITTEN DESCRIPTION
The Written Description Issue
The Examiner found that the claims are directed to methods of using
any agent that acts as an antagonist to the α1dAR, and that such a genus
would include any small molecule inhibitor of α1dAR, a variety of
oligonucleotide therapeutics, peptide inhibitors, and antibodies. (Ans. 4.)
The Examiner found that the Specification did not describe such a broad
genus, and that the Specification’s disclosure of one known small molecule
inhibitor, Prazosin, and a cDNA sequence corresponding to α1dAR did not
provide a representative sample of structures describing the broad genus.
(Id. at 5.) According to the Examiner, Applicants may not patent “an
invention that is not considered to be in their possession at the time of
filing.” (Id. at 4-5.)
Appellant contends that the “[A]pplication makes it clear that, at the
time of filing, Appellant had possession of a variety of types of α1dAR
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antagonists suitable for use in treating irritative symptoms.” (App. Br. 10.)1
“Further, the disclosure includes an extensive discussion of assays that could
be used to identify small molecule antagonists.” (Id.) Appellant disputes
the Examiner’s reliance on the Rochester case, arguing that the active agent
in the claims here “is not defined by the effect sought.” (Id. at 11.)
The issues with respect to this rejection are:
did the Specification describe as broad a variety of antagonists as
claimed;
did the disclosure of assays for identifying antagonists describe the
antagonists;
do the claims define the antagonist used in the claimed method by the
effect sought?

Findings of Fact
1. The claimed method includes a step administering “an α1d-adrenergic
receptor (α1dAR) antagonist.” (Claim 1.)
2. “[A]n α1d-adrenergic receptor (α1dAR) antagonist” denotes a genus of
compounds.
3. The Specification does not explicitly define the compounds in the
genus.
4. The Examiner found that the genus “antagonist” includes “any small
molecule inhibitor of α1dAR, . . . other peptide inhibitors, and
antibodies.” (Ans. 4.)

1 Citations are to the “Amended Appeal Brief” filed April 25, 2008.
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5. The Specification mentions the known AR antagonist prazosin.
(Spec. 3:22.)
6. The Specification mentions the known radiolabeled AR antagonist
[125I]HEAT. (Id. at 5:7-13.)
7. The Specification mentions the selective ligand BMY7378 but does
not identify it as an AR antagonist. (Id. at 6:7-8.)
8. The Specification indicates that a compound found to bind in a
screening assay is “potentially” an antagonist. (Id. at 7:5-7.)
9. “To determine the specific effect of any particular test compound
selected on the basis of its ability to bind α1dAR, various assays can be
used including IP assays . . . and bladder (e.g. human bladder) smooth
muscle contraction assays . . . .” (Id. at 10:18-22.)
10. “Compounds suitable for use in treating irritative symptoms will be
associated with antagonistic (inhibitory) effects in the IP assay and
contraction inhibitory effects in the contraction assay.” (Id. at 22-24.)
11. Antibodies specific for α1dAR “can be formulated as pharmaceutical
compositions and used therapeutically as α1dAR antagonists.” (Id. at
11:13-15.)
12. The Specification discloses that α1dAR oligonucleotide and antisense
constructs can be used to treat irritative symptoms. (Id. at 16-24.)

Principles of Law Relating to Written Description
When an Applicant claims a class of compounds or materials, the
Applicant “must describe that class in order to meet the description
requirement of the statute.” In re Lukach, 442 F.2d 967, 968 (CCPA 1971).
A description of what a material does, rather than of what it is, usually does
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not suffice. Regents of the Univ. of Cal. v. Eli Lilly & Co., 119 F.3d 1559,
1568 (Fed. Cir. 1997).
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.

Univ. Of Rochester v. G.D. Searle & Co., Inc., 358 F.3d 916, 926 (Fed. Cir.
2004). “[W]here no explicit description of a generic invention is to be found
in the specification . . . mention of representative compounds may provide
an implicit description upon which to base generic claim language.” In re
Robins, 429 F.2d 452, 456-57 (CCPA 1970).

Analysis of the Written Description Issue
As to Appellant’s first issue, the evidence of record is that Appellant
had possession of the antagonists Prazosin, [125I]HEAT, and a cDNA
corresponding to α1dAR at the time of filing. The Specification did not
provide an explicit definition of the genus “α1dAR antagonist,” and
Appellant does not dispute the Examiner’s finding that the genus α1dAR
antagonist necessarily includes other small molecules, peptides, antibodies,
and other molecules, none of which were named or described. Appellant
offers no evidence that a person of skill in the art would credit Prazosin,
[125I]HEAT, and the one disclosed cDNA as describing the genus α1dAR
antagonist.
A written description of the genus of compositions to be used in a
method could be achieved by (i) a description of a representative number of
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compositions falling within the genus, or (ii) a recitation of distinguishing
structural features common to members of the genus, which features
constitute a substantial portion of the genus. See e.g., Eli Lilly, 119 F.3d at
1568 (“A written description of an invention involving a chemical genus,
like a description of a chemical species, ‘requires a precise definition, such
as by structure, formula, [or] chemical name,’ of the claimed subject matter
sufficient to distinguish it from other materials.”). Although the statute does
not require representative species, “where no explicit description of a
generic invention is to be found in the specification . . . mention of
representative compounds may provide an implicit description upon which
to base generic claim language.” Robins, 429 F.2d at 456-57. In other
words, representative species “are a means by which certain requirements of
the statute may be satisfied.” Id.
A representative number of species could be described by a
“disclosure of sufficiently detailed, relevant identifying characteristics,”
such as “complete or partial structure, other physical and/or chemical
properties, functional characteristics when coupled with a known or
disclosed correlation between function and structure, or some combination
of such characteristics.” Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d
956, 964 (Fed. Cir. 2002). Thus, an additional way to describe a genus
could be (iii) reliance on a known or disclosed correlation between function
and structure. See e.g., Amgen, Inc. v. Hoechst Marion Roussel, Inc.,
314 F.3d 1313, 1332 (Fed. Cir. 2003) (“the requirement may be satisfied if
in the knowledge of the art the disclosed function is sufficiently correlated to
a particular, known structure”). Appellant offered no evidence or
explanation that the disclosure met any of these tests, or that it described the
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genus in another way. Finding no explicit or implicit description of the
genus, we agree with the Examiner that the genus of antagonists to be used
in the method was not described.
As a second issue, Appellant argues that the disclosure of assays for
identifying antagonists sufficed to describe antagonists that would be
identified. We disagree. The assays test compounds in two stages. (FF8-
10.) A first assay determines if a compound binds the receptor as a
“potential” antagonist, and a second assay determines if a potential
antagonist identified in the first assay actually inhibits (i.e., antagonizes) in a
biological assay. Until a compound passes both tests, it is unknown whether
the test compound is an antagonist. Appellant offers no evidence that a
person of skill in the art would accept the Specification’s description of the
two-stage assay as descriptive of the genus of antagonists to be used in the
method of treatment. We find that Appellant was not in possession of the
genus at the time the Application was filed. “This is exactly the type of
overreaching the written description requirement was designed to guard
against.” Purdue Pharma L.P. v. Faulding Inc., 230 F.3d 1320, 1327 (Fed.
Cir. 2000).
Like the Examiner, we find Rochester determinative here and we are
not persuaded by Appellant’s third argument. Appellant argues that
Rochester is inapt because the antagonists to be used in Appellant’s method
are not defined by the effect sought. (App. Br. 11.) That is, the effect
sought in Appellant’s claims is “treating,” and the compound to be used is
not defined in terms of the “treating” effect. (Id.) Instead, the compound to
be used is “an α1d-adrenergic receptor (α1dAR) antagonist.” (Id.) We find
this distinction makes no real difference because the word “antagonist” has
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only a functional meaning in claim 1 as something that antagonizes or
inhibits the receptor. The functional word does not serve to define the genus
because it does not distinguish the genus from other molecules except by
function. See Eli Lilly, 119 F.3d at 1568. One skilled in the art cannot
visualize or recognize the identity of other members of the genus. 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. Id.;
accord, Holland Furniture Co. v. Perkins Glue Co., 277 U.S. 245, 257-58
(1928) (“the attempt to broaden product claims by describing the product
exclusively in terms of its use or function is subject to the same vice as is the
attempt to describe a patentable device or machine in terms of its function”).
Finally, Appellant did not disclose a correlation between the function
of antagonizing α1dAR and the structure of the broad class “antagonist,”
other than for antisense oligonucleotides. Claims 9 and 10 use nucleic acid
molecules, and are not subject to this rejection. The oligonucleotide
antagonists are disclosed to function by inhibiting production of α1dAR or
encoding a molecule that inhibits production of α1dAR. Appellant does not
offer any evidence that those of ordinary skill in the art would accept the
oligonucleotide disclosure as descriptive of the broader antagonist class to
be used in claim 1. If there was any pre-existing knowledge in the art of a
relevant correlation that could have supplemented the Specification’s
deficiency, Appellant provided no evidence of it, e.g., correlating antisense
oligonucleotides to other kinds of inhibitors. There is nothing in the record
establishing that those of skill in the art would have understood Appellant’s
oligonucleotide disclosure to correlate to possession of methods using other
kinds of antagonists.
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As in Rochester, the claims are directed to a process for
accomplishing a desired result using a composition having a specified
functional property. Here the generic phrase “α1dAR antagonist” does not
define structural features of the compounds that distinguish them from other
compounds.
Claims 2-8 were not been argued separately and therefore fall with
claim 1. 37 C.F.R. § 41.37(c)(1)(vii).

ENABLEMENT
The Enablement Issue
The Examiner’s position is that the Specification “does not provide
sufficient guidance or appropriate examples that would enable a skilled
artisan to use the disclosed [oligonucleotide] compounds or methods of
using said compounds in in vivo environments.” (Ans. 6.) The Examiner
found that the state of antisense treatment, as evidenced by five articles in
the scientific literature, was that (1) predicting inhibitory activity of an
antisense molecule was difficult, (2) uptake of oligonucleotides into target
cells was not likely to be efficient, (3) non-antisense effects, such as
undesireable immunostimulatory activity, were unpredictable, (4) it was
challenging to obtain a therapeutic effect, and (5) there was a likelihood that
in vitro studies would not always predict in vivo efficacy. (Id. at 7-10.) The
Examiner found the Specification’s prophetic examples gave insufficient
guidance to resolve the unpredictable areas, and concluded that the claimed
method was not enabled. (Id. at 13-14.)
Appellant contends that (i) exemplification is not required to satisfy
the enablement requirement, and (ii) the publications the Examiner relied on
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“are not related to treatment of irritative symptoms associated with bladder
and lower urinary tract diseases.” (App. Br. 12, emphasis omitted.)
The issues with respect to this rejection are:
did the Examiner require examples; and
did the publications establish a reason to doubt the Specification was
enabling?
Findings of Fact
13. The Specification instructs that oligonucleotide or antisense constructs
can be delivered “using any of a variety of approaches,” including
instillation into the bladder, systemically, via viral vectors, or via liposomes.
(Spec. 12:1-10.)
14. According to the Specification, “[o]ne skilled in the relevant art can
readily optimize the dose and treatment regimen.” (Id. at 10-13.)
15. According to Braasch, “[i]n practice over the last decade . . . gene
inhibition by antisense oligomers has not proven to be a robust or generally
reliable technology.” (4503, ¶ 1.)
16. Braasch reports that more recent results with Fomivirsen, Genasense,
and ISIS 3521 “are encouraging because they indicate that oligonucleotides
can enter human tumors in vivo and have a favorable impact on disease
progression.” (4506, left col.)
17. Braasch further writes that “[s]ince the pharmacokinetic properties of
oligonucleotides are likely to be similar regardless of oligonucleotide
sequence, progress in the Genasense and ISIS 3521 trials encourages the
belief that it will be possible to target many other genes successfully.” (Id.)
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18. Braasch reports that “[e]xperience in the clinic is demonstrating that
even older generation oligonucleotide designs are effective drugs . . . .”
(4509, last para.)
19. Gewirtz reports that antisense technology “has been found to be
highly variable in its efficiency.” (3161, middle col.)
20. According to Agrawal, “[t]he specificity and application of antisense
oligonucleotides have been strongly validated in animal models for various
disease targets.” (Abstract.)
21. Tamm reports that “[o]ne antisense drug has been approved for local
treatment of cytomegalovirus-induced retinitis, and several antisense
oligonucleotides are in clinical trials, including oligonucleotides that target
the mRNA of BCL2, protein-kinase-C alpha, and RAF kinase.” (Abstract.)
22. According to Tamm, “[v]arious other targets in the field of oncology
have been analysed in vitro and in animals . . . with encouraging results
(panel 1).” (490, left col.)
23. Tamm reports that “[t]he number of clinical trials ongoing represents
a growing interest in antisense technology (panel 2).” (490, right col.)
24. According to Tamm, “results suggest that the principle of antisense
works, not only with local treatment, as shown with fomivirsen, but also
with systematic treatment with antisense oligonucleotides.” (495, left col.)
25. Branch reports that “[t]he time and expense necessary to screen large
numbers of potential antisense molecules and ribozymes, and to carefully
monitor their in vivo effects, raise the stakes for those seeking to use them as
genetic probes.” (50, left col.)
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26. According to Branch, “there is growing evidence that antisense
molecules can be useful pharmacological tools when applied carefully.”
(Id.)
Principles of Law Relating to Enablement
The first paragraph of 35 U.S.C. § 112 requires that the specification
teach persons skilled in the art to make and use the invention without undue
experimentation. In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988). A lack
of enablement rejection is appropriate where the written description fails to
teach those in the art to make and use the invention as broadly as claimed
without undue experimentation. In re Cortright, 165 F.3d 1353, 1356 (Fed.
Cir. 1999). “The PTO cannot make this type of rejection, however, unless it
has reason to doubt the objective truth of the statements contained in the
written description.” Id. at 1357.

Analysis of the Enablement Issue
Appellant’s first argument relating to the enablement issue is that
“exemplification is not required.” (App. Br. 12.) The Examiner pointed to
the lack of examples as “a legitimate factor in determining lack of
enablement, especially when the art is of an unpredictable nature,” citing In
re Wands. (Ans. 13.) We agree that the presence or absence of examples is
a legitimate factor for consideration with respect to enablement. We
understand the Examiner’s explanation of deficiencies in the disclosure are
not a requirement for examples, but are an observation that examples might
have filled the gaps the Examiner perceived. Appellant’s first argument
does not help to resolve whether the Examiner appropriately weighed the
available evidence.
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Appellant’s second argument is that the publications the Examiner
relied on are not related to treating bladder symptoms. (App. Br. 12.) The
publications concern experience with antisense therapy generally. All five
publications indicate that antisense therapy works, albeit not efficiently, and
they discuss various challenges in achieving success. (FF1-12.) The
Examiner focused on the difficulties mentioned in the publications. We
agree that the publications proffered by the Examiner, while not directly
related to treating bladder symptoms, do relate more broadly to the
administration of antisense compounds within the scope of the claim and
establish that this art requires much screening and careful monitoring.
(FF25.) However, Appellant provided the cDNA sequence needed for
making antisense molecules. We are not persuaded that screening candidate
antisense molecules from the cDNA sequence disclosed, and carefully
monitoring their performance, would be undue experimentation in this field.
The literature indicates this is the nature of the art, and that careful
monitoring is required. See Wands, 858 F.2d at 740 (screening many
hybridomas to find useful ones was not undue experimentation in that art).

CONCLUSIONS OF LAW
Written Description
The Specification did not explicitly or implicitly describe the genus of
antagonists to be used as claimed;
the disclosure of assays for identifying antagonists did not describe
the antagonists; and
claims 1-8 define the antagonist to be used in the claimed method by
the function of antagonizing or inhibiting, i.e., by an effect sought.
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Enablement
The Examiner did not issue a requirement for examples; and
the publications did not establish a reason to doubt the Specification
was enabling.

SUMMARY
We affirm the rejection of claims 1-8 under 35 U.S.C. § 112, ¶ 1, for
lack of compliance with the written description requirement; and
we reverse the rejection of claims 1-10 under 35 U.S.C. § 112, ¶ 1, for
lack of compliance with the enablement requirement.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

AFFIRMED-IN-PART

cdc

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