Ex Parte Aoki et al

Patent Trial and Appeal Board

Jun 17, 2016

11959134 (P.T.A.B. Jun. 17, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
111959,134 12/18/2007
51957 7590 06/21/2016
ALLERGAN, INC
2525 DUPONT DRIVE, T2-7H
IRVINE, CA 92612-1599
FIRST NAMED INVENTOR
K. Roger Aoki
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www .uspto.gov
ATTORNEY DOCKET NO. CONFIRMATION NO.
16952-CONS (BOT) 2233
EXAMINER
GUPTA, ANISH
ART UNIT PAPER NUMBER
IPLA
NOTIFICATION DATE DELIVERY MODE
06/21/2016 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address( es):
patents_ip@allergan.com
pair_allergan@firsttofile.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte K. ROGER AOKI, MICHAEL W. GRA YSTON,
STEVEN R. CARLSON, and JUDITH M. LEON
Appeal2013-002207
Application 11/959, 134
Technology Center 1600
Before JEFFREY N. FREDMAN, ULRIKE W. JENKS, and
RYAN H. FLAX, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal1'2 under 35 U.S.C. § 134 involving claims to a
method for treating a neuromuscular disease, disorder or condition with a
botulinum toxin. The Examiner rejected the claims as obvious and on the
grounds of obviousness-type double patenting. We have jurisdiction under
35 U.S.C. § 6(b). We affirm.
1 Appellants identify the Real Party in Interest as Allergan, Incorporated (see
App. Br. 1).
2 This Appeal is related to Appeals 2013-002211, 2013-002212, 2013-
002213, 2013-002214, and Ex ParteAoki, 2011WL5080231(BPAI2011),
aff'd 562 Fed. Appx. 976 (mem.) (Fed. Cir. 2014) (Rule 36).
Appeal2013-002207
Application 11/959,134
STATEMENT OF THE CASE
Background
"Botulinum toxins, in particular Botulinum toxin type A, has been
used in the treatment of a number of neuromuscular disorders and
conditions" (Spec. 1 :32-34). "[S]even immunologically distinct
[Botulinum] neurotoxins have been identified. These have been given the
designations A, B, C, D, E, F and G" (Spec. 2:32-34). "Botulinum toxin
type A, the toxin type generally utilized in treating neuromuscular
conditions, is currently available commercially from several sources" (Spec.
4:12-14).
The Claims
Claims 1-12 are on appeal. Independent claim 1 is representative3
and reads as follows:
1. A method for treating a neuromuscular disease, disorder
or condition, \'I/herein said method is a human medical
application and comprises the step of administering to a human
patient with a neuromuscular disease, disorder or condition an
effective amount of the neurotoxic component of a botulinum
toxin, wherein the neurotoxic component has a molecular weight
of about 150 kilodaltons, thereby treating the disease, disorder or
condition.
3 "Claims 1-12 stand or fall together" (App. Br. 4).
2
Appeal2013-002207
Application 11/959,134
The Issues
I. Claims 1-12 were rejected under 35 U.S.C. § 103(a) as obvious
over Seiffl and Tse5 (Final Act. 2-3).
II. Claims 1--4 were rejected under 35 U.S.C. § 103(a) as obvious
over Clark6 and Tse (Final Act. 3-5).
III. Claims 1--4 were rejected under 35 U.S.C. § 103(a) as obvious
over Jankovic7 and Tse (Final Act. 5-6).
IV. Claims 1--4 were rejected on the grounds of obviousness-type
double patenting over claims 1--4 of Aoki '9928 and Tse (Final Act. 7-8).
V. Claims 1--4 were rejected on the grounds of obviousness-type
double patenting over claims 1-14 of Aoki '365 9 and Tse (Final Act. 9-10).
VI. Claims 1--4 were rejected on the grounds of obviousness-type
double patenting over claims 1--4 of Aoki '47610 and Tse (Final Act. 10-11).
4 S. R. Seiff et al., Use of botulinum toxin to treat blepharospasm in a 16-
year-old with a dystonic syndrome, 5 PEDIATRIC NEUROL. 121-23 (1989)
(Abstract only) (hereinafter "Seiff').
5 Chun K. Tse et al., Preparation and Characterisation of Homogeneous
Neurotoxin Type A from Clostridium botulinum, 122 EUR. J. BIOCHEM. 493-
500 (1982) (hereinafter "Tse").
6 Jonathan B. Clark, Cervical Dystonia Following Exposure to High-G
Forces, 61 AVIAT. SPACE ENVIRON. MED. 935-37 (1990) (hereinafter
"Clark").
7 Joseph Jankovic et al., Therapeutic uses of Botulinum Toxin, 324 NEW
ENGLAND J. MED. 1186-94 (1991) (hereinafter "Jankovic").
8 Aoki et al., US 6,776,992 B2, issued Aug. 17, 2004 (hereinafter "Aoki
'992").
9 Aoki et al., US 6,458,365 Bl, issued Oct. 1, 2002 (hereinafter "Aoki
'365").
10 Aoki et al., US 6,887,476 B2, issued May 3, 2005 (hereinafter "Aoki
'476").
3
Appeal2013-002207
Application 11/959,134
VII. Claims 1--4 were rejected on the grounds of obviousness-type
double patenting over claims 1-7 of Aoki '610 11 and Tse (Final Act. 12-13).
Because all of these rejections tum on the same issue, we will
consider them together.
The Examiner finds that Seiff, Clark, Jankovic, Aoki '992, Aoki '365,
Aoki '4 7 6, and Aoki '610 each teach treatment of neuromuscular disorders
with haemagglutinin-complexed botulinum toxin but do "not teach the use
of the pure neurotoxin free of hemagglutinin" (Final Act. 3; cf id. at 4, 6, 8,
9, 11, and 12; FF 1-5).
However, the Examiner finds that Tse teaches that the neurotoxic
component of type A botulinum "specifically and characteristically inhibited
stimulated and spontaneous release of acetylcholine at the vertebrate
neuromuscular junction" (Final Act. 3; FF 9) in the same manner as the
complexed toxin, and also, "when injected into the hind leg muscle of a rat,
produced local paralysis within 24 hours" (id.; FF 8).
The Examiner concludes that the ordinary artisan would have found it
obvious "to use the pure toxin of Tse to treat[] severe blepharospasm and
facial grimacing, because Tse teaches that pure toxin has similar activity in
the paralysis of muscles as complexed neurotoxin" (Final Act. 3). The
Examiner finds "a reasonable expectation of success because both the pure
toxin and the complexed toxin have similar activity against spontaneous
release of acetylcholine" (id.).
11 Aoki et al., US 6,869,610 B2, issued Mar. 22, 2005 (hereinafter "Aoki
'610").
4
Appeal2013-002207
Application 11/959,134
ISSUE
Has the Examiner established that treating neuromuscular disease by
administering the neurotoxic component of a botulinum toxin, rather than a
complexed form of the botulinum toxin, would have been obvious over the
evidence of record?
FINDINGS OF FACT
1. Seiff teaches "intradermal injections of botulinum A toxin
greatly reduced the spasms and improved function. No side effects were
observed. Local botulinum A toxin injections may be useful in the
treatment of eyelid and facial spasms in patients with generalized dystonias"
(Seiff, abstract).
2. Clark teaches that "[r]ecently, another available treatment has
proven quite successful. Botulinum A toxin injected locally into affected
muscles relieves the sustained contracture observed in dystonias" (Clark
936, col. 1 ).
3. J ankovic teaches that the "beneficial effects of injections of
botulinum toxin in the treatment of blepharospasm have been demonstrated
in one controlled and several open trials" (Jankovic 1188, col. 1; internal
citations omitted).
4. Aoki '992 claim 1 recites: "A method for treating a tension
headache pain, the method comprising the step of subcutaneous
administration of a therapeutically effective amount of a botulinum toxin to
a head or neck location of a patient, thereby relieving tension headache
pain." (Aoki '992, claim 1; cf Aoki '365, claim 1 "method for treating
5
Appeal2013-002207
Application 11/959,134
tension headache"; Aoki '4 7 6, claim 1 "method for treating pain associated
with a muscle disorder").
5. Aoki '610 claim 1 recites: "A method for alleviating neuralgia,
the method comprising the step of peripheral administration of an effective
amount of a botulinum toxin to a human patient for a time effective to
alleviate neuralgia pain, wherein the pain treated is not associated with a
headache." (Aoki '610, claim 1).
6. Tse describes removal of the immunogenic haemagglutinin
component of the type A haemagglutinin-neurotoxin complex, and
characterization of the isolated, purified 150 kD neurotoxic component (Tse
493, col. 2; 494, cols. 1-2; 496, col. 2; 499, col. 2).
7. Tse teaches that the "purified neurotoxin ... is homogeneous
by all criteria tested including dodecyl sulphate gel electrophoresis under
non-reducing conditions, isoelectric focussing and immunodiffusion" (Tse
499, col. 2).
8. Tse teaches that "[w]hen this neurotoxin (5 mouse LDso units;
60 pg protein) was injected into rat hind-leg muscle, it produced local
paralysis within 24 h" (Tse 498, col. 1 ).
9. Tse teaches that "[a]s clearly demonstrated with impure
neurotoxin complexes ... , pure neurotoxin specifically and
characteristically inhibited stimulated and spontaneous release of
acetylcholine at the vertebrate neuromuscular junction" (Tse 499, col. 2
(internal citations omitted)).
6
Appeal2013-002207
Application 11/959,134
10. Schantz12, cited by Appellants, discusses the properties of
botulinum toxins, including the purified neurotoxic component. According
to Schantz:
The nontoxic proteins bound to the neurotoxin apparently play
an important role in maintaining the toxic shape of the
neurotoxin. Careful handling of purified toxin is therefore
important for maintenance of stability. Botulinum toxin type A
is readily denatured by heat at temperatures above 40°C,
particularly at alkaline pH. Solutions of the toxin lose toxicity
when bubbles form at the air/liquid interface causing stretching
and pulling of the neurotoxin out of its toxic shape. This
denaturation also takes place in an atmosphere of nitrogen or
carbon dioxide. Dilution to extremely low concentrations
(nanograms per milliliter) also tends to decrease the stability of
the neurotoxin, but this can be prevented by diluting with a
buffered solution (at pH 6.8 or below) containing another protein
such as gelatin and certain albumins such as bovine or human
serum albumin. When the pH is raised above 7 .3, the neurotoxin
is liberated, which is very labile. Because of its lability the
neurotoxin is not practical for medical applications.
(Schantz 82, col. 2, internal citations omitted).
11. Schantz teaches:
Most recent information concerning the structure and
pharmacology of botulinum toxin has been obtained with
purified neurotoxins, but it is unlikely that these will be used in
a clinical setting. The toxin complexes are much more stable
than neurotoxins and can be diluted and formulated with
retention of toxicity. Pure neurotoxins can be kept for several
12 Edward J. Schantz & Eric A. Johnson, Properties and Use of Botulinum
Toxin and Other Microbial Neurotoxins in Medicine, 56 MICROBIOL. REV.
80-99 (1992) (hereinafter "Schantz").
7
Appeal2013-002207
Application 11/959,134
weeks to months in solution in the cold but are inactivated on
dilution, formulation, and drying.
(Schantz 89, col. 2).
12. Schantz teaches that "we recommend that fresher batches of
toxin periodically be prepared to avoid detrimental changes that may occur
on aging .... Diluting a solution of botulinum toxin type A from a
concentration of 1 or 2 mg/ml to nanogram concentrations causes
detoxification unless another protein is added for protection" (Schantz 83,
col. 2).
13. DasGupta13 teaches that the "pure NT is stable for months at pH
7.9 and 4°C" and teaches that the neurotoxin:
isolated from the complex by ion-exchange chromatography,
first reported in 1966 (16) and now routinely prepared in various
laboratories (73, 48), has stable activity; Williams et al. (81) have
found that the homogenous preparation of type A NT, stored at
4°C in 0.15 M TRIS/HCl buffer, pH 7.9, is stable for several
months. The pure preparations NT types A and E at very low
concentrations (such as 1 x 10-10 Mand lower) in physiological
buffers, with and without added gelatin or serum albumin, are
highly active (25, 48, 59, 73, 86) ....
REFERENCES
16. DasGupta BR, Boroff DA, Rothstein E. Chromatographic
fractionation of crystalline toxin of Clostridium botulinum
type A, Biochem Biophys Res Commun 1966;22:750-
756.
13 Bibhuti R. DasGupta, Structures of Botulinum Neurotoxin, Its Functional
Domains, and Perspectives on the Crystalline Type A Toxin, in Therapy with
Botulinum Toxin 15-39 (J. Jankovic ed. 1994) (hereinafter "DasGupta").
8
Appeal2013-002207
Application 11/959,134
48. Tse CK, Dolly JO, Hambleton P, Wray D, Melling J.
Preparation and characterization of homogenous
neurotoxin type A from Clostridium botulinum. Its
inhibitory action on neuronal release of acetylcholine in
the absence and presence of f3-bungaro toxin. Eur J
Biochem 1982; 122:493-500.
59. Lomneth R, Suszkiw JB, DasGupta BR. Response of the
chick ciliary ganglion-iris neuromuscular preparation to
botulinum neurotoxin. Neurosci Lett 1990;113:211-216.
73. Sugii S, Sakaguchii G. Molecular construction of
Clostridium botulinum type A toxins. Infect Immun
1975; 12: 1262-1270.
81. Williams RS, Tse CK, Dolly JO, Hambleton P, Melling J.
Radioiodination of Botulinum Neurotoxin Type A with
Retention of Biological Activity and Its Binding to Brain
Synaptosomes. Eur. J. Biochem. 1983; 131 :437--445.
(DasGupta 31-32, 35-39).
14. Lamanna14 1988 discloses "a purified sample of type A toxin
free of hemagglutinin ... dissolved in a sterilized phosphate-0.2% gelatin
buffer (pH 6.2----6.7) for storage and i.v. injection" into mice, rats, and dogs
(Lamanna 1988 70).
15. Lamanna 1988 teaches that "[h]emagglutinin-free toxin had the
same qualitative effects on the heart" as hemagglutinin-containing (i.e.,
complexed) toxin, but was more potent than the hemagglutinin-containing
toxin on a weight to weight basis (Lamanna 1988 72).
14C. Lamanna et al., Cardiac Effects of Botulinal Toxin, 293 Arch. Int.
Pharmacodyn. Ther. 69-83 ( 1988) (hereinafter "Lamanna 1988").
9
Appeal2013-002207
Application 11/959,134
16. The Specification's only disclosure regarding the neurotoxic
component is reproduced below:
The neurotoxic component of Botulinum toxin has a
molecular weight of about 150 kilodaltons and is thought to
comprise a short polypeptide chain of about 50 kD which is
considered to be responsible for the toxic properties of the toxin,
i.e., by interfering with the exocytosis of acetylcholine, by
decreasing the frequency of acetylcholine release, and a larger
polypeptide chain of about 100 kD which is believed to be
necessary to enable the toxin to bind to the presynaptic
membrane.
(Spec. 3, 11. 9-16).
PRINCIPLES OF LAW
[O]bviousness must be determined in light of all the facts, and
there is no rule that a single reference that teaches away will
mandate a finding of nonobviousness. Likewise, a given course
of action often has simultaneous advantages and disadvantages,
and this does not necessarily obviate motivation to combine. See
[Winner Int'! Royalty Corp. v. Wang, 202 F.3d 1340, 1349 n.8
(Fed. Cir. 2000)] ("The fact that the motivating benefit comes at
the expense of another benefit, however, should not nullify its
use as a basis to modify the disclosure of one reference with the
teachings of another. Instead, the benefits, both lost and gained,
should be weighed against one another."). Where the prior art
contains "apparently conflicting" teachings (i.e., where some
references teach the combination and others teach away from it)
each reference must be considered "for its power to suggest
solutions to an artisan of ordinary skill .... consider[ing] the
degree to which one reference might accurately discredit
another." In re Young, 927 F.2d 588, 591 (Fed. Cir. 1991).
Medichem, S.A. v. Rolabo, S.L.,437 F.3d 1157, 1165 (Fed. Cir. 2006).
10
Appeal2013-002207
Application 11/959,134
DISCUSSION
We adopt the Examiner's findings of fact and reasoning regarding the
scope and content of the prior art (Final Act. 2-13; FF 1-16) and agree that
the claims are obvious over the cited prior art. We address Appellants'
arguments below.
Appellants contend that "the Schantz et al. reference clearly
discourages use of the neurotoxic component for human therapeutic
purposes" (App. Br. 9) and that the Board "ignores the plain, express
language of the Schantz et al. reference" (App. Br. 10). Specifically,
Appellants argue that the following statements in Schantz teach away from
the claimed method:
Because of its lability the neurotoxin is not practical for medical
applications.
(Schantz 82, col. 2; App. Br. 13 (emphasis Appellants')).
Most recent information concerning the structure and
pharmacology of botulinum toxin has been obtained with
purified neurotoxins, but it is unlikely that these will be used in
clinical settings. The toxin complexes are much more stable than
neurotoxin and can be diluted and formulated with retention of
toxicity. Pure neurotoxins can be kept for several weeks to
months in solution in the cold but are inactivated on dilution,
formulation, and drying.
(Schantz 89, col. 2; App. Br. 13 (emphasis Appellants')).
In support of this argument, Appellants submitted the Declaration of
Dr. Leonard A. Smith, whose work "has involved production, formulation,
and characterization of native botulinum toxin and recombinant neurotoxin
11
Appeal2013-002207
Application 11/959,134
component fragments" (Deel. I 15 , i-f 9). Dr. Smith concludes that "a person
having ordinary skill in the art reading Schantz 1992 and considering the Tse
et al. reference ... with or without consideration of the Lamanna [1988 and
1993] references clearly would have been discouraged from using the
neurotoxic component for human therapeutic purposes" based, at least in
part, on the statements quoted above (Deel. III16, i-f 4).
There are, however, substantive and compelling inconsistencies
between Deel. I and Deel. III. Deel. I states that "[t]here is no doubt in my
mind and it is my opinion that the statements in Schantz 1992 that the
neurotoxic component is 'not practical for medical applications" and that the
neurotoxic component 'is unlikely .. (to) .. be used in a clinical setting' are
clearly wrong" (Deel. I, i-f 15), while Deel. III states:
[ w ]hen considering all the facts presented in paragraph 15 of my
First Declaration with the exception of those from the DasGupta
reference and the Goodnough thesis, I conclude that a person
having ordinary skill in the art would not have considered the
statements within Schantz 1992 to be clearly wrong.
(Deel. III, ,-r 4; cf Deel. II 17, ,-r 4). Deel. III excludes the DasGupta reference
from the analysis, apparently because DasGupta itself is not prior art (see
Deel. III, i-f 3), but DasGupta was a review article that relied upon Williams,
a prior art reference, to evidence the stability of the purified neurotoxic
15 Declaration of Leonard A. Smith, PhD. (dated Nov. 20, 2007) (hereinafter
"Deel. I").
16 Declaration of Leonard A. Smith, PhD. (dated Dec. 16, 2011) (hereinafter
"Deel. III").
17 Declaration of Leonard A. Smith, PhD. (dated May 25, 2011) (hereinafter
"Deel. II").
12
Appeal2013-002207
Application 11/959,134
component (FF 13; cf Ans. 24) as well as a number of additional references
that teach neurotoxin isolation (FF 13).
Because the statements in Deel. II and III are inconsistent with Deel.
I, and Deel. II and III fail to consider the prior art teachings of Williams
relied upon by DasGupta, we find those statements' credibility reduced and
we afford them less weight. See Scripps Clinic & Res. Found. v. Genentech,
Inc., 927 F.2d 1565, 1578 (Fed. Cir. 1991) ("[A]pparent inconsistencies
among the three [expert] declarations raise questions of credibility and
weight").
We have, nonetheless, carefully considered Dr. Smith's Declarations.
However, we do not agree that Schantz teaches away from substituting the
neurotoxic component of botulinum toxin for the haemagglutinin-complexed
form of the toxin used by Seiff, Clark, Jankovic, and the Aoki patents. That
is, we do not agree that Schantz would have led one of ordinary skill in the
art to expect that the purified neurotoxin would be ineffective in treating
neuromuscular disorders, as there is ample evidence of record that the
complexed toxin and the purified neurotoxic component both produce the
desired effect-local paralysis (FF 1-5, 8), and both operate by the same
mechanism (FF 9). While we agree that one of ordinary skill in the art
would have concluded from the Schantz reference that the purified toxin is
less practical in comparison with the complexed toxin, Schantz also teaches
that the purified neurotoxin can be stored for weeks in the cold, and can be
successfully diluted with careful buffering and handling (FF 11-12)-
which is not unusual for therapeutic agents.
13
Appeal2013-002207
Application 11/959,134
Appellants contend that "the Board and the Examiner appear to
somehow base their various obviousness rejections for this family of
applications on the teachings of the Lamanna publications. As the record
indicates, the Lamanna references, however, are not cited in the current
obviousness rejections" (App. Br. 11 ), but Appellants also note that "[ w ]hen
assessing obviousness, the prior art as a whole including any evidence of
teaching away must be considered. Medichem v. Rolabo, 437 F.3d 1157,
1166 (Fed. Cir. 2005)" (App. Br. 17 (emphasis Appellants')).
We agree with Appellants that the prior art must be assessed as a
whole in combination with the entirety of the evidence of record including
the Smith Declarations and the teachings of the Specification in order to
assess the overall power to suggest solutions to an artisan of ordinary skill.
We also agree with Appellants that no special weight is provided to
references relied upon by the Examiner (see App. Br. 17)18.
"When prior art contains apparently conflicting references, the Board
must weigh each reference for its power to suggest solutions to an artisan of
ordinary skill." In re Young, 927 F.2d 588, 591 (Fed. Cir. 1991). Moreover,
Although a reference that teaches away is a significant factor to
be considered in determining unobviousness, the nature of the
teaching is highly relevant, and must be weighed in substance. A
known or obvious composition does not become patentable
simply because it has been described as somewhat inferior to
some other product for the same use.
In re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994).
18 With regard to Appellants' citation of an unrelated, nonprecedential PT AB
decision (see App. Br. 14--16), we note that "[ e Jach case must be decided on
its own merits." In re Gyurik, 596 F.2d 1012, 1016 (CCPA 1979).
14
Appeal2013-002207
Application 11/959,134
Lamanna 1988 is part of the record and prior art as a whole. Indeed,
the Examiner cites Appellants' own Reply Brief filed on February 24, 2009
in U.S. Application 10/933,723 that the "Lamanna and DasGupta
publication provide evidence that at the time the '996 parent application was
filed, purified neurotoxic component had been isolated, formulated, and
stored in stable form. Moreover, these publications provide evidence that
the neurotoxic component is sufficiently stable and active to be
administered intravenously" (Ans. 24; emphasis in original). Lamanna
1988, a prior art reference, supports this position, evidencing the storage and
use of the purified neurotoxin component for treatment of animals (FF 14).
Lamanna 1988 also found that the purified neurotoxin component was more
potent than the hemagglutinin-containing toxin on a weight to weight basis
(FF 15). These teachings support the Examiner's position that the ordinary
artisan, weighing the teachings of the different references, would have had
reason to use the purified neurotoxin component as more potent, and would
have had a reasonable expectation of success in storing and using the
purified neurotoxin (FF 14--15).
When we consider the Schantz reference as a whole, together with the
Seif, Clark, Jankovic, Tse, Lamanna 1988, and Aoki references, we are not
persuaded that one of ordinary skill in the art would have been dissuaded
from substituting the neurotoxic component of botulinum toxin for the
larger, more immunogenic haemagglutinin-complexed form of the toxin in
the prior art methods of treating neuromuscular disorders.
The Court of Customs and Patent Appeals has concluded that "[when
an] advantage is not disclosed in appellant's application" he is "not in a
15
Appeal2013-002207
Application 11/959,134
favorable position to urge it as a basis for the allowance of claims." In re
Herr, 304 F.2d 906, 909 (1962) (internal citation and quotations omitted).
The Herr reasoning, though addressed to unexpected results and not
obviousness per se, is apt here, where the Specification has a single, limited
disclosure relating to the existence of a neurotoxic component of botulinum
toxin (FF 16), but provides no disclosure whatsoever on methods of
purifying the neurotoxic component, methods of stably storing a purified
neurotoxic component, or any clinical method for using the purified
neurotoxic component. In sum, the Specification provides no express
guidance on how to make or use "an effective amount of the neurotoxic
component" as required by claim 119, fully relying upon the prior art to
enable and disclose this teaching.
Thus, to the extent that Appellants rely upon the purified neurotoxic
component as a distinguishing limitation, their own Specification is solely
enabled for patient administration of a purified neurotoxic component by the
prior art, not by any teachings disclosed by Appellants.
19 We note, but do not rely upon, the absence of any requirement in claim 1
for purification of the neurotoxic component. This would have provided the
Examiner a reasonable basis to interpret claim 1 broadly to encompass
botulinum toxin including both the neurotoxic component and
haemagglutinin component, consistent with the Specification's reliance
solely on commercially available botulinum toxin that includes both
components and the absence of any disclosure in the Specification teaching
purifying the neurotoxic component. Under this claim interpretation, which
we do not rely upon, the primary references would have anticipated claim 1
(see Spec. 8, 11. 22-25).
16
Appeal2013-002207
Application 11/959,134
Appellants contend that "DasGupta specifically corroborates
Appellant[s'] position that Schantz would have discouraged one of ordinary
skill from clinical use of the neurotoxic component" citing Das Gupta's
teaching that "this prevailing view needs rectification" (Reply Br. 3 citing
DasGupta 31 (emphasis Appellants'.)) Appellants contend:
[i]f a person having ordinary skill in the art as of December
1993 already knew that Dr. Schantz's statements were incorrect
as the Examiner repeatedly insists is the case, then the statements
within the DasGupta reference are nonsensical as there would
have been no prevailing view needing rectification as of 1994.
(Reply Br. 4).
We do not find this argument persuasive because DasGupta is not
relying upon newly disclosed post filing date evidence from 1994, but rather
expressly relies upon prior art references to establish the functionality of the
purified neurotoxin, specifically stating:
\Villiams et al. (81) have found that the homogeneous
preparation of type A NT, stored at 4°C in 0.15 M TRIS-HCl
buffer, pH 7.9, is stable for several months. The pure
preparations of NT types A and E at very low concentrations
(such as 1 x 10-10 Mand lower) in physiological buffers, with
and without added gelatin or serum albumin, are highly active
(25,48,59 '73 ,86).
(DasGupta 32). As already noted, Williams was published in 1983 (FF 13).
The other references cited by DasGupta were published from 1966 to 1990
(FF 13) and reasonably establish that DasGupta was relying on knowledge in
prior art regarding storage and use of the purified neurotoxin, not post-filing
date information.
17
Appeal2013-002207
Application 11/959,134
CONCLUSION OF LAW
The Examiner has established that treating neuromuscular disease by
administering the neurotoxic component of a botulinum toxin, rather than a
complexed form of the botulinum toxin, would have been obvious over the
evidence of record.
SUMMARY
In summary, we affirm all of the obviousness and obviousness-type
double patenting rejections.
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
18