Ex Parte Schiffman

Board of Patent Appeals and Interferences

Sep 18, 2008

10379157 (B.P.A.I. Sep. 18, 2008)

UNITED STATES PATENT AND TRADEMARK OFFICE
_________________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
_________________

Ex parte RHETT M. SCHIFFMAN

APPELLANT
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Appeal 2008-4607
Application 10/379,157
Application Publication 2004/0175399
Technology Center 1600

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Decided: September 18, 2008
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Before SALLY GARDNER LANE, MICHAEL P. TIERNEY, and JAMES
T. MOORE Administrative Patent Judges.

LANE, Administrative Patent Judge.

DECISION ON APPEAL

Appeal 2008-4607
Application 10/379,157

I. STATEMENT OF THE CASE
The appeal is from a Final Rejection of claims 10 and 17-23. Claims
1-9, 11-16, and 24-33 are also pending in the application, but have been
withdrawn. (App. Br. 5). 35 U.S.C. § 134. We have jurisdiction under 35
U.S.C. § 6(b). We reverse and enter a new ground of rejection.
The application was filed March 3, 2003. It was published on
September 9, 2004, as Application Publication 2004/0175399 (“Pub.
2004/0175399”). The real party in interest is said to be Allergan, Inc. (App.
Br. 3).
The Examiner rejected claims 10 and 17-23 under 35 U.S.C. § 102(e)
over U.S. Patent No. 6,831,059 (“Donovan”), which was filed March 15,
2001, and issued December 14, 2004. The Examiner also relied on the
following references as evidence of anticipation:
• Bramley et al., “Human Placental Gonadotrophin-Releasing
Hormone (GNRH) Binding Sites: III. Changes in GnRH
Binding Levels with Stage of Gestation,” Placenta, vol. 15, 733
(1994).
• Dgani1 et al., “Clinical-pathological study of uterine
leiomyomas with high mitotic activity,” Acta Obstet. Gynecol.
Scand., vol. 77, pp. 74-77 (1998).
• Eidne et al., “Gonadotropin-Releasing Hormone (GnRH)-
Binding Sites in Human Breast Cancer Cell Lines and

1 The Examiner and Appellant refer to this reference as “Dqani,” but the
name of the first author is Dgani.
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Inhibitory Effects of GnRH Antagonists,” J. Clin. Endocrinol.
Metab., vol. 64, pp. 425-32 (1987).
• Sion-Vardi et al., “Gonadotropin-Releasing Hormone Specific
Biding Sites in Normal and Malignant Renal Tissue,” J. Urol.,
vol. 148, pp. 1568-70 (1992).
• Vilos, “Uterine fibroids :relationships to reproduction,”
Minerva Ginecologica, vol. 55, pp. 417-423 (2003).
• Volpe et al., “Pregnancy following regression of uterine
submucosal leiomyoma with GnRH therapy; a case report,”
Eur. J. Obstet. & Gynecol., vol. 39, pp. 223-25 (1991).
• Wiznitzer, “Gonadotropin-Releasing Hormone Specific
Binding Sites in Uterine Leiomyomata,” Biochem. Biophys.
Res. Comm., vol. 152, pp. 1326-31 (1988).
Appellant appeals the rejection of claims 10 and 17-23 under 35
U.S.C. § 102(e) over Donovan. Appellant argue separately for the
patentability of claims 21-23. (App. Br. 15-16).
II. FINDINGS OF FACT
The record supports the following findings of fact as well as any other
findings of fact set forth in this opinion, by at least a preponderance of the
evidence.
1. Appellant’s claim 10 recites:
A method for treating a uterine fibroid, the method comprising
the step of local administration of between about 10-3 U/kg2 and

2 Although Appellant’s Claims Appendix recited this term to be “10-3
U/kg,” we understand it to be “10-3 U/kg.”

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about 2000 U/kg of a botulinum toxin to a uterine fibroid,
thereby treating a uterine fibroid.

(App. Br., Claims Appx. 18).
2. Appellant’s specification provides that “[t]he botulinum toxin is
selected from the group consisting of botulinum toxins types A, B, C, D, E,
F and G . . . .” (Pub. 2004/0175399 ¶ [0100]; see also Pub. 2004/0175399
¶¶ [0105], [0110], [0131], [0133]; [0143], and [0144]).
3. Appellant’s specification acknowledges that “it has been
disclosed that targeted botulinum toxins (i.e. with a non-native binding
moiety) can be used to treat various conditions (see e.g. U.S. Pat. No
5,989,545, as well as WO 96/33273; WO 99/17806; WO 98/07864; WO
00/57897; WO 01/21213; WO 00/10598.” (Pub. 2004/0175399 ¶ [0042]).
4. Appellant’s specification does not limit “a botulinum toxin” as
excluding a “non-native binding moiety.”
5. Donovan teaches that “[t]hose skilled in this art will also
appreciate that an agent of this invention may also be administered to treat
medical conditions which will benefit from a decrease of gonadotrophin
levels in the body.” (Donovan col. 17, ll. 41-44).
6. Donovan teaches:
GnRH antagonists and agonists have proven effective in the
treatment of certain conditions which require a reduction of
gonadotrophin release. For example, they have proven effective
in the treatment of endometriosis, uterine fibroids, polycystic
ovarian disease, precocious puberty and several gonadal
steroid-dependent neoplasia, most notably cancers of the
prostate, breast and ovary.

(Donovan col. 1, ll. 56-62).
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7. Donovan teaches treating patients with “an agent [that]
comprises a light chain component, a translocation component, and a
targeting component.” (Donovan col. 12, ll. 30-32; see also Donovan
Examples 1-5, col. 20, l. 45, through col. 22, l. 32).
8. The light chain taught in Donovan “may include a light chain of
a botulinum toxin, a butyricum toxin, a tetani toxin or biologically active
variants of these toxins.” (Donoavn col. 12, ll. 34-36).
9. The translocation component taught in Donovan comprises a
heavy chain or modified heavy chain of botulinum toxin. (Donovan col. 12,
ll. 60-66).
10. The “targeting component of [Donovan] is able to bind to a
specific target cell receptor, for example, a GnRH receptor, preferably the
pituitary GnRH receptor.” (Donovan col. 14, ll. 8-11).
11. Donovan teaches that “[f]or agents employing a natural,
mutated or recombinant botulinum toxin A comprising the therapeutic,
translocation and targeting component, an effective dose of an agent to be
administered may be about 1 U to about 500 U of the botulinum toxin.”
(Donovan col. 17, ll. 51-55).
12. Donovan teaches “‘Local administration’ means direct
administration of a pharmaceutic at or to the vicinity of a site on or within an
animal body, at which site a biological effect of the pharmaceutic is desired.
Local administration excludes systemic routes of administration, such as
intravenous or oral administration.” (Donovan col. 10, ll. 1-6).
13. Donovan teaches that
The routes of administration of the present invention include,
but are not limited to, direct injection into the central nervous
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system. . . . Other routes of administration include, without
limitation, transdermal, peritoneal, subcutaneous,
intramuscular, intravenous and intrarectal.

(Donovan col, 18, ll. 3-19)
14. Donovan does not expressly teach local administration of an
agent into a uterine fibroid.
15. Donovan asserts that the botulinum toxin agent (called “LHN-
GnRH”) is effective in the treatment of endometriosis, prostate cancer,
precocious puberty, endometrial cancer, and breast cancer, when
administered locally to the pituitary gland. (See Donovan col. 20, l. 43,
through col. 22, l. 31).
16. Wiznitzer teaches “Gonadotropin-releasing hormone (GnRH)
analogs can cause regression of uterine leiomyomata [fibroids] . . . . These
results indicate, for the first time, the presence of specific binding sites for
GnRH in uterine leiomyomata, suggesting a direct effect of GnRH analogs
on this tissue.” (Wiznitzer abstract).
17. Wiznitzer does not use an agent that includes any part of the
botulinum toxin.
18. Appellant’s claim 21 recites:
The method of claim 10, wherein treating the uterine fibroid
further reduces the distortion of the endometrial cavity.

(App. Br., Claims Appx. 18).

19. Vilos states that “[f]rom the available evidence it can be
concluded that removal of fibroids that distort the uterine cavity may be
indicated in infertile women . . . .” (Vilos 419, first col., second paragraph).
20. Appellant’s claim 22 recites:
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The method of claim 10, wherein treating the uterine fibroid
further reduces the frequency of miscarriages.

(App. Br., Claims Appx. 18).

21. Volpe states: “In a patient harboring…leiomyomas, adversely
affecting conception and pregnancy outcome, GnRHa
[gonadotropin/releasing hormone analog] treatment may be an initial
approach . . . .” (Volpe abstract).
22. Volpe does not use an agent that includes any part of the
botulinum toxin.
23. Appellant’s claim 23 recites:
The method of claim 10, wherein treating the uterine fibroid
further prevents the fibroid from becoming malignant.

(App. Br., Claims Appx. 18).

24. Dgani states: “The benign clinical behavior of such tumors
supports their current designation as mitotically active leiomyomas, thus
deleting the previous misnomer ‘smooth muscle tumors of uncertain
malignant potential.’” (Dgani abstract).

III. LEGAL PRINCIPLES
Claimed subject matter is anticipated by the teachings of a reference
only if the claimed subject matter is identically disclosed or described by the
teachings of the reference. Richardson v. Suzuki Motor Co., Ltd., 868 F.2d
1226, 1236 (Fed. Cir. 1989) (citation omitted) (“The identical invention
must be shown in as complete detail as is contained in the patent claim.”).
To be anticipated, the claimed subject matter must be disclosed “clearly and
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unequivocally” in the reference. In re Arkley, 455 F.2d 586, 587 (C.C.P.A
1972) (“Thus, for the instant [anticipation] rejection… to have been proper,
the ….reference must clearly and unequivocally disclose the claimed
compound or direct those skilled in the art to the compound without any
need for picking, choosing, and combining various disclosures not directly
related to each other by the teachings of the cited reference.”).
On the other hand, “[w]hen a work is available in one field of
endeavor, design incentives and other market forces can prompt variations of
it, either in the same field or a different one. If a person of ordinary skill can
implement a predictable variation, § 103 likely bars its patentability.” KSR
Int’l Co. v. Teleflex, Inc., 127 S.Ct. 1727, 1740 (2007). “Common sense
teaches . . . that familiar items may have obvious uses beyond their primary
purposes, and in many cases a person of ordinary skill will be able to fit the
teachings of multiple patents together like pieces of a puzzle.” Id. at 1742.
IV. ANALYSIS
Appellant’s claim 10 recites:
A method for treating a uterine fibroid, the method comprising
the step of local administration of between about 10-3 U/kg and
about 2000 U/kg of a botulinum toxin to a uterine fibroid,
thereby treating a uterine fibroid.

(FF3 1). While Appellant’s specification provides that “[t]he botulinum
toxin is selected from the group consisting of botulinum toxins types A, B,
C, D, E, F and G . . . ” (FF 2), it also acknowledges that “it has been
disclosed that targeted botulinum toxins (i.e. with a non-native binding

3 Finding of Fact.
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moiety) can be used to treat various conditions . . . .” (FF 3). Appellant’s
specification does not limit “a botulinum toxin” to excluding “non-native
binding moieties.” (FF 4). “During examination, ‘claims ... are to be given
their broadest reasonable interpretation consistent with the specification, and
. . . claim language should be read in light of the specification as it would be
interpreted by one of ordinary skill in the art.’” In re American Academy of
Sci. Tech Center, 367 F.3d 1359, 1364 (Fed. Cir. 2004) (ciation omitted).
Thus, the claim term “a botulinum toxin” includes botulinum toxins of types
A, B, C, D, E, F, and G, either alone or with an attached “non-native binding
moiety.”
Donovan teaches that “[t]hose skilled in this art will . . . appreciate
that an agent of this invention may also be administered to treat medical
conditions which will benefit from a decrease of gonadotrophin levels in the
body.” (FF 5). In regard to the conditions that would benefit from a
decrease in gonadotrophin levels, Donovan teaches that GnRH antagonists
and agonists “have proven effective in the treatment of endometriosis,
uterine fibroids, polycystic ovarian disease, precocious puberty and several
gonadal steroid-dependent neoplasia, most notably cancers of the prostate,
breast and ovary.” (FF 6).
Donovan teaches treating patients with “an agent [that] comprises a
light chain component, a translocation component, and a targeting
component.” (FF 7). The light chain and translocation components can be
the light chain and heavy chain, respectively, of botulinum toxin (FFs 8 and
9), while the targeting component can bind to a GnRH receptor (FF 10).
Donovan teaches that “an effective dose of an agent to be
administered may be about 1 U to about 500 U of the botulinum toxin” (FF
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11), which overlaps with the claimed range of “between about 10-3 U/kg and
about 2000 U/kg . . . .” (FF 1). Donovan teaches “local administration” of
the agent, wherein “‘[l]ocal administration’ means direct administration of a
pharmaceutic at or to the vicinity of a site on or within an animal body, at
which site a biological effect of the pharmaceutic is desired. Local
administration excludes systemic routes of administration, such as
intravenous or oral administration.” (FF 12). Donovan does not expressly
teach administration of an agent into a uterine fibroid. (FF 14). The
Examiner has not pointed us to any teaching in Donovan that “‘clearly and
unequivocally’ directs those skilled in the art to make this selection nor any
indication that [the prior art] ever made the selection [itself].” Arkley, 455
F.2d at 588. Thus, we conclude that Donovan does not clearly and
unequivocally disclose the claimed method of treating a uterine fibroid with
a botulinum toxin without any need for picking, choosing, and combining
various disclosures. Accordingly, we reverse the rejection under 35 U.S.C.
§ 102(e) over Donovan.
On the other hand, while Donovan acknowledges that GnRH
antagonists and agonists are effective in treating uterine fibroids (FF6),
Wiznitzer teaches that the GnRH analogs known at the time may act directly
on the fibroid (FF 16). Thus, those of skill in the art would have had reason
to combine their teachings to administer the botulinum toxin agents of
Donovan, which Donovan asserts are effective when administered to the
pituitary gland (FF 15), directly to uterine fibroid tissue. There would have
been a reasonable expectation of success in this method because Donovan
teaches local administration of botulinum toxin agents. (FFs 12 and 13).
Those of skill in the art would have been able to “implement a predictable
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variation,” KSR, supra, of the methods expressly taught in Donovan, in light
of the teaching of Wiznitzer, and Appellant’s claimed methods would have
been obvious. Accordingly, we enter a new ground of rejection for claims
10 and 17-23 under 35 U.S.C. § 103(a) over Donovan and Wiznitzer.
Turning to the arguments that apply to our new grounds of rejection
under 35 U.S.C. § 103(a), Appellant first argued that
[a] person of ordinary skill in the art would not consider
botulinum toxin to be a GnRH agonist or antagonist. As the
Donovan specification explains, GnRH antagonists are existing
drugs that act to decrease gonadotrophin secretion by binding
competitively to the GnRH receptors. (Donovan at column 1,
lines 45-46, 53-55) Although recombinant and chemically
modified botulinum toxin is used to create the therapeutic agent
claimed in Donovan, the botulinum toxin does not bind to the
GnRH receptor. (Id. at columns 12 through 14) The targeting
component of the agent, not the botulinum toxin, is the moiety
which binds the receptor. (Id. at column 14, lines 8-12)[.]

(App. Br. 13; see also Reply Br. 5). Appellant’s specification acknowledges
that native botulinum toxin can be modified with non-native binding
moieties (FF 3), and neither Appellant’s specification nor claim 10 limits the
claim term “a botulinum toxin” to exclude these moieties (see FFs 1 and 4).
See American Academy, supra.
In regard to claims 21-23, Appellant argued that the claimed subject
matter, methods to reduce distortion of the endometrial cavity, frequency of
miscarriages, and the prevention of a fibroid from becoming malignant,
respectively, is not disclosed in Donovan. (App. Br. 15). Appellant
asserted, further, that
"When the claimed composition or machine is disclosed
identically by the reference, an additional reference may be
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relied on to show that the primary reference has an 'enabled
disclosure."' In re Donohue, 766 F.2d 531, 226 USPQ 619, 621
(Fed. Cir. 1985). In the instant case, the claimed subject matter
disclosed in claims 21-23 is not identically disclosed by
Donovan and therefore, the cited extrinsic evidence [Vilos,
Volpe, and Dgani] cannot be relied on to show that the primary
reference anticipates the claimed subject matter.

(App. Br. 15-16). The Examiner did not cite Vilos, Volpe, and Dgani to
show that Donovan is enabled, but instead to show that those of skill in the
art would have known that the claimed effects are “effects generally
achieved by any treatment of uterine fibroids that inhibits their growth and
further development and/or causes their regression.” (Ans. 17). These
references serve the same function under our new grounds of rejection.
Vilos states that “removal of fibroids that distort the uterine cavity
may be indicated in infertile women . . . .” (FF 19), thus providing evidence
that those in the art knew that treatment of a fibroid would “[reduce] the
distortion of the endometrial cavity” (FF 18), as claimed. Appellant argued
that “Vilos does not qualify as a prior art reference under 35 U.S.C. § 102
because it was not published until October 2003, seven months after the
earliest priority date of the present application.” (App. Br. 15). References
that are not technically prior art are still properly cited to establish the level
of ordinary skill in an art at and around the time of the present invention.
See In re Erlich, 22 U.S.P.Q.2d 1463, 1465 (BPAI 1992). Appellant has not
provided us with any evidence to convince us that those in the art first
learned that fibroids distort the endometrial cavity less than seven months
before Vilos was published. Thus, those of skill in the art would have used
the agents taught in Donovan to treating fibroids and thus reduce the
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distortion of the endometrial cavity they cause, after combining the
teachings of Donovan and Wiznitzer.
Volpe discloses that gonadotropin/releasing hormone analog treatment
is an initial approach to treating uterine fibroids that adversely affect
conception and pregnancy outcome, that is miscarriages (FF 21),
demonstrating that those of skill in the art would have used the botulinum
toxin agent in Donovan, which is a GnRH analog because it binds to a
gonadotrophin receptor (FF 10), to “[reduce] the frequency of miscarriages.”
(FF 20), after combining the teachings of Donovan and Wiznitzer.
Finally, Dgani states: “The benign clinical behavior of such tumors
supports their current designation as mitotically active leiomyomas, thus
deleting the previous misnomer ‘smooth muscle tumors of uncertain
malignant potential.’” (FF 24). Thus, after combining the teachings of
Donovan and Wiznitzer, those of skill in the art would have used the
botulinum toxin of Donovan to prevent a uterine fibroid from “becoming
malignant,” as claimed (FF 23), as part of the overall treatment of the uterine
fibroid.
Accordingly, claims 21-23 are not separately patentable under the new
grounds of rejection under 35 U.S.C. § 103(a) over Donovan and Wiznitzer.

V. ORDER
Upon consideration of the record and for the reasons given, the
Examiner’s rejection of claims 10 and 17-23 under 35 U.S.C. § 102(e) over
Donovan, as evidenced by Vilos, Volpe, Dgani, and/or Wiznitzer is
REVERSED;
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We enter a new grounds of rejection for claims 10 and 17-23 under 35
U.S.C. § 103(a) over Donovan and Wiznitzer for the reasons set forth herein.
37 C.F.R. § 41.50(b).
37 C.F.R. § 41.50(b) provides that, “[a] new grounds of rejection
pursuant to this paragraph shall not be considered final for judicial review.”
37 C.F.R. § 41.50(b) also provides that the Appellants, WITHIN
TWO MONTHS FROM THE DATE OF THE DECISION, must exercise
one of the following two options with respect to the new grounds of
rejection to avoid termination of proceedings as to the rejected claims:
(1) Submit an appropriate amendment of the claims so rejected or new
evidence relating to the claims so rejected, or both, and have the matter
reconsidered by the examiner, in which event the proceeding will be
remanded to the examiner; or
(2) Request that the proceeding be reheard under 37 C.F.R. § 41.52 by
the Board upon the same record.

REVERSED; NEW GROUNDS ENTERED 37 C.F.R. § 41.50(b)

ak

Stephen Donovan
Allergan, Inc.
T2-7H
2525 Dupont Drive
Irvine, CA 92612

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