Ex Parte Borodic

Board of Patent Appeals and Interferences

Sep 15, 2008

09382837 (B.P.A.I. Sep. 15, 2008)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
____________

Ex parte GARY E. BORODIC
____________

Appeal 2008-24521
Application 09/382,837
Technology Center 1600
____________

Decided: September 15, 2008
____________

Before DONALD E. ADAMS, LORA M. GREEN, and JEFFREY N.
FREDMAN, Administrative Patent Judges.

ADAMS, Administrative Patent Judge.

DECISION ON APPEAL

This appeal under 35 U.S.C. § 134 involves claims 1, 5-8, 10-12, 24,
25, and 42-57, the only claims pending in this application (App. Br. 2). We
have jurisdiction under 35 U.S.C. § 6(b).

1 Heard August 13, 2008.

Appeal 2008-2452
Application 09/382,837

INTRODUCTION
The claims are directed to a method of reducing inflammation (claims
1, 5-8, 50, 54, and 55); a method for treating allergic blepharoconjunctivitis
(claims 10-12, 42-45, 52, and 53); and a method for treating inflammation
(claims 24, 25, 46-49, 51, 56, and 57). Claims 1, 10 and 12 are illustrative:
1. A method of reducing inflammation, comprising the step of
administering a therapeutically effective dose of a botulinum toxin to an
affected area of a subject suffering from inflammation, wherein the
botulinum toxin reduces at least one symptom of inflammation, and wherein
said therapeutically effective dose is sufficient to reduce said at least one
symptom of inflammation but less than a dose necessary to produce
substantial muscle weakness within the affected area.

10. A method for treating allergic blepharoconjunctivitis comprising
the step of administering a therapeutically effective dose of a botulinum
toxin in a periocular area of a subject suffering from blepharoconjunctivitis,
thereby reducing inflammation.

12. A method [for treating classic type 1 hypersensitivity comprising
the step of administrating a botulinum toxin to an affected area of a subject
suffering from classic type 1 hypersensitivity, thereby reducing
inflammation], wherein the hypersensitivity is hay fever, rhinitis, allergic
rhinitis, allergic forms of eczema, urticaria, rheumatoid arthritis,
inflammatory bowel disease, or asthma.

The Examiner relies on the following prior art references to show
unpatentability:
First US 6,063,768 May 16, 2000
The MERCK MANUAL of DIAGNOSIS AND THERAPY (MERCK) pp.
318-320, 1308-1311, and 2368 (sixteenth ed., Robert Berkow et al., eds,
MERCK Research Laboratories, Rahway, N.J. 1992).

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The rejections as presented by the Examiner are as follows:
1. Claims 1, 5-8, 24, 25, 42, 43, and 46-57 stand rejected under the
enablement provision of 35 U.S.C. § 112, first paragraph.
2. Claims 1, 5-8, 10-12, 24, 25, and 42-57 stand rejected under the written
description provision of 35 U.S.C. § 112, first paragraph.
3. Claims 10-12 stand rejected under 35 U.S.C. § 103(a) as unpatentable
over the combination of First and MERCK.
We reverse the rejections under the enablement and written
description provisions of 35 U.S.C. § 112, first paragraph.
We affirm the rejection of claims 10-12 under 35 U.S.C. § 103(a) as
unpatentable over the combination of First and MERCK. However, because
our rationale differs from that of the Examiner we affirm the rejection as a
new ground of rejection. 37 C.F.R. § 41.50(b).

FINDINGS OF FACT (FF)
1. Appellant discloses “that the use of botulinum toxin in doses from 1/3rd
to several orders of magnitude less than those associated with treatment
of regional movement diseases has been effective to reduce
inflammation and adverse sensory experiences associated with the
inflammatory response” (Spec. 4-5).
2. Appellant discloses that “botulinum toxin in low dosages [in the range
from 0.5-5 units] are effective anti-inflammatory agents. Typical
minimum effective doses range from 0.5-5 units as opposed to 20-600
units used for treatment of movement disorders” (Spec. 5). Appellant
discloses that a dosage range of 0.6 - 15 units is “lower than that
required to produce regional [muscle] weakness” (Spec. 20).
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3. First teaches a method wherein “at least one serotype or a combination
of serotypes of Botulinum neurotoxin either alone or in combination
with other peptides or fusion proteins” are “administered in a safe and
effective amount, [to] antagonize and therefore decrease or block
inflammation induced by the neurogenic mechanisms underlying or
associated with inflammatory disorders” (First, Abstract).
4. First teaches that “[a] neurogenic disorder involves the release of
neuropeptides, neuromodulators and other mediators of the neurogenic
response including mediators from the immune nervous and endocrine
systems” (First, col. 2, ll. 56-59).
5. First teaches that “[t]he present invention provides a method of treating
or inhibiting diseases or syndromes with an underlying or associated
neurogenic component (neurogenic disorder) by way of antagonizing
the actions of neurogenic mediators involved in the disorder” by
administering botulinum toxin in “a safe and effective amount . . . at or
near the site of inflammation” (First, col. 5, ll. 15-19; col. 7, ll. 32-35).
6. First teaches that the method antagonizes “the release or enzymati [sic],
cleave neuropeptides, neurotransmitters and other mediators from, in
particular, sensory afferent or efferent neurons, autonomic efferent
nerves or secretory cells” (First, col. 1, ll. 19-22).
7. First teaches that “[t]he responses mediated by the peptides and
transmitters released from sensory nerves include vasodilatation (via
cGRP release), and increased vascular permeability (via SP [(Substance
P)2] release)” (First, col. 2, ll. 33-36).

2 See First, col. 3, l. 3.
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8. First teaches that “the activation of the immune system initiates the
attraction of white cells, activation of phagocytic function of
neutrophils and macrophages, stimulation of the increased production
and release of inflammatory mediators from these cells and the
degranulation of mast cells and local release of histamine” (First, col. 2,
ll. 39-44).
9. First teaches that
Substance P has been shown to stimulate the release of
prostaglandin E2 and collagenase from cells in joints of patients
with rheumatoid arthritis . . ., and further, induce the release of
immune-active agents such as interleukin 1, tumor necrosis
factor and interleukin 6. . . . The result of this neuroendocrine
cascade of events has been termed, neurogenic inflammation . .
. and works as a central network modulating the events between
the immune, nervous and endocrine systems. A neurogenic
disorder involves the release of neuropeptides, neuromodulators
and other mediators of the neurogenic response including
mediators from the immune nervous and endocrine systems.

(First, col. 2, ll. 47-59.)
10. First teaches that “SP and cGRP are both released from afferent sensory
neurons that carry sensory information back to the central nervous
system” (First, col. 3, ll. 64-66).
11. First hypothesizes that botulinum neurotoxin “acts enzymatically to
cleave either proteins such as SNAP-25, syntaxin, and synaptobrevin,
which are critical to vesicular release or direct cleavage of
inflammatory mediators including but not limited to SP, CGRP,
PACAP, VIP” (First, col. 4, ll. 6-11).
12. First teaches that an “example whereby neurogenic inflammation takes
place is in airway diseases, such as asthma, in which inflammatory
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mediators such as cGRP and SP play a major role in the inflammatory
process” (First, col. 4, ll. 57-60).
13. First teaches that the
“[d]osage of the toxin is dependent on the area or condition that
is to be treated. This could be as high as 1000 U but a more
useful range of 5-500 LD50s of botulinum neurotoxin alone or
in combination with other toxins, fusion proteins, peptides, or
in combination with compounds such as capsaicin, may be
more suitable. However higher or lower doses may be
necessary.

(First, col. 7, ll. 22-28.)

14. MERCK teaches that Type I hypersentivity reactions involve antigens
(allergens) that combine with specific IgE Antibodies that are bound to
membrane receptors on tissue mast cells and blood basophiles
(MERCK 318: 30-31).
15. MERCK teaches that this antibody (Ab) - antigen (Ag) “reaction causes
the release of potent vasoactive and inflammatory mediators” (MERCK
318: 31-32).
16. MERCK teaches that Type I hypersensitivity reactions include allergic
rhinitis, conjunctivitis, and asthma” (MERCK 319: 21).
17. MERCK teaches that Blepharitis is the inflammation of the eyelid
margins (MERCK 2368: 13).
18. Appellant discloses that allergic blepharoconjunctivitis involves
“conjunctival and lid margin erythema, itching and ocular mucous
discharge associated with ocular irritation” (Spec. 16).

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DISCUSSION
1. Claims 1, 5-8, 24, 25, 42, 43, and 46-57 stand rejected under the
enablement provision of 35 U.S.C. § 112, first paragraph.
The Examiner finds that Appellant’s Specification provides an
enabling description of “a method of reducing allergy induced conjunctivitis
in a mouse comprising administering a botulinum toxin”, but does not
provide an enabling description of “a method of reducing inflammation
without causing muscle weakness” (Ans. 5). We disagree for the reasons the
reasons set forth in Appellant’s Brief (App. Br. 9-14).
However, to be complete, we recognize the Examiner’s assertion that
in all of “the human examples [in Appellant’s Specification] the toxin is
used in at least a dosage of 2.5 units . . . a dosage specifically intended to
cause muscle weakness and the anti-inflammatory properties are merely
observed as a side effect (see particularly Case I and Case II)” (Ans. 6). The
human studies reported in Case I and Case II utilize a dosage of 2.5 units
and 5 units of botulinum toxin per injection site respectively (Spec. 11 and
12). Contrary, to the Examiner’s factually unsupported assertion, Appellant
discloses that this dosage is lower than that required to produce regional
muscle weakness (FF 1 and 2; App. Br. 10). Therefore, while the Examiner
asserts that “[n]o where at pages 10 -20 [sic] does the specification disclose
that Appellant actually measured for the claimed invention, i.e., a method of
reducing inflammation without causing muscle weakness” (Ans. 13), the
Examiner makes no attempt to provide an evidentiary basis to rebut
Appellant’s presumptively accurate disclosure. In re Marzocchi, 439 F.2d
220, 224 (CCPA 1971).
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It is the Examiner who has the initial burden of establishing a prima
facie case of non-enablement. The burden of proof does not shift to
Appellant until the Examiner first meets his burden. Marzocchi, 439 F.2d at
223-224. For the foregoing reasons, we find that the Examiner has not met
his burden of establishing a prima facie case of non-enablement.
Accordingly, the rejection of claims 1, 5-8, 24, 25, 42, 43, and 46-57 under
the enablement provision of 35 U.S.C. § 112, first paragraph is reversed.

2. Claims 1, 5-8, 10-12, 24, 25, and 42-57 stand rejected under the written
description provision of 35 U.S.C. § 112, first paragraph.
While the Examiner asserts that Appellant’s disclosure fails to
adequately describe the claimed invention, the Examiner’s statement of the
rejection fails to identify or explain, with any degree of particularity, exactly
what is not adequately described or the legal theory upon which the
Examiner relies to support the rejection (see Ans. 8-10). It is not until the
Examiner responds to the arguments presented in Appellant’s Brief that the
Examiner explains his position with any degree of particularity.
Nevertheless, for the reasons set forth in Appellant’s Brief we are not
persuaded by the Examiner’s assertions on this record (see App. Br. 20-37).
Accordingly, we reverse the rejection of claims 1, 5-8, 10-12, 24, 25,
and 42-57 under the written description provision of 35 U.S.C. § 112, first
paragraph.

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3. Claims 10-12 stand rejected under 35 U.S.C. § 103(a) as unpatentable
over the combination of First and MERCK.
First teaches a method to decrease or block inflammation induced by
neurogenic mechanisms underlying or associated with inflammatory
disorders by administering a safe and effective amount of Botulinum
neurotoxin to antagonize the actions of neurogenic mediators involved in the
disorder (FF 3-7 and 13; see generally Ans. 4). Appellant does not dispute
and therefore concedes to this teaching in First. 3 Appellant does not dispute
and therefore concedes to First’s teaching that the immune system initiates,
inter alia, the release of inflammatory mediators; and that a neurogenic
disorder involves the release of mediators from, inter alia, the immune
system (FF 8-9). Appellant does not dispute and therefore concedes to
First’s teaching that Substance P stimulates the release of immune-active
agents resulting in a neuroendocrine cascade of events termed, neurogenic
inflammation, and works as a central network modulating the events
between the immune, nervous and endocrine systems; and that botulinum
neurotoxin antagonizes this cascade of events (FF 9-11).
Appellant does, however, assert that First “differs from the claimed
invention because it does not teach a method of reducing inflammation due
to blepharoconjunctivitis, hay fever, rhinitis, or type 1 hypersensitivity[,] . . .
allergic forms of eczema, urticaria or inflammatory bowel disease” (Reply
Br. 6).

3 Arguments not made are waived. See 37 C.F.R. § 41.37(c)(1)(vii) (“Any
arguments or authorities not included in the brief or a reply brief ... will be
refused consideration by the Board, unless good cause is shown.”).
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MERCK teaches that Type I hypersensitivity reactions involve
allergens and causes the release of vasoactive and inflammatory mediators
(FF 14-15). MERCK teaches that Type I hypersensitivity reactions include
allergic rhinitis, conjunctivitis, and asthma (FF 16). First teaches that
neurogenic inflammation takes place, inter alia, in asthma, wherein
inflammatory mediators such as cGRP and SP play a major role in the
inflammatory process (FF 12). Taken together, the combination of First and
MERCK teach that asthma is a Type I hypersensitivity reaction that falls
within the genus of neurogenic inflammation that is treatable by the
administration of botulinum toxin.
MERCK teaches that Blepharitis is an inflammation of the eyelid
margins and Appellant acknowledges that allergic blepharoconjunctivities
involves both the conjunctival and lid margin (FF 17-18). Stated differently,
blepharoconjunctivitis is the combination of conjunctivitis with blepharitis.
Absent evidence to the contrary, of which there is none, we find that like
asthma, conjunctivitis is a Type I hypersensitivity reaction that falls within
the genus of neurogenic inflammation that is treatable by the administration
of botulinum toxin as taught by First.
While Appellant does not provide an explicit statement of the claim
groupings, it appears that Appellant has separately argued claims 10 and 12
(see App. Br. 19). Accordingly, we limit our discussion to claims 10 and 12.
Claim 11 will stand or fall together with claim 12. 37 C.F.R.
§ 41.37(c)(1)(vii).

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Claim 10:
Claim 10 is drawn to a method for treating allergic
blepharoconjunctivitis, which is combination of conjunctivitis with
blepharitis. The claimed method comprises the single step of administering
a therapeutically effective dose of a botulinum toxin in a periocular area of a
subject suffering from blepharoconjunctivitis, thereby reducing
inflammation. According to Appellant, the combination of First and
MERCK fails to teach or suggest “‘allergic blepharoconjunctivitis’ or ‘a
periocular area’ as required by claim 10” (App. Br. 19). We disagree.
As discussed above, absent evidence to the contrary, of which there is
none, we find that conjunctivitis is a Type I hypersensitivity reaction that
falls within the genus of neurogenic inflammation as taught by First. By
reducing the inflammation of the conjunctivitis the inflammation in a subject
suffering from blepharoconjunctivitis is reduced. In addition, First teaches a
method of treating neurogenic inflammation by administering botulinum
toxin at or near the site of inflammation (FF 5). For allergic
blepharoconjunctivitis, the site of inflammation would be a periocular area.
For the foregoing reasons, we are not persuaded by Appellant’s
argument that the “specific limitations recited in the claim[ ] are not taught
in the references” (App. Br. 19). Express teachings directed to the specific
subject matter of a claim are not required to reach a conclusion of
obviousness. KSR Int’l. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007). As
on this record,
the teaching, motivation, or suggestion may be implicit from
the prior art as a whole, rather than expressly stated in the
references. . . . The test for an implicit showing is what the
combined teachings, knowledge of one of ordinary skill in the
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art, and the nature of the problem to be solved as a whole would
have suggested to those of ordinary skill in the art.

In re Kahn, 441 F.3d 977, 987-988 (Fed. Cir. 2006). Stated differently, “a
court can take account of the inferences and creative steps that a person of
ordinary skill in the art would employ.” KSR, 127 S. Ct. at 1741.
On reflection, we find that the preponderance of the evidence on this
record supports a conclusion that the claimed method would have been
prima facie obvious to a person of ordinary skill in the art at the time the
invention was made. For the foregoing reasons, we are not persuaded by
Appellant’s assertion that KSR is inapplicable to the facts on this record
(Reply Br. 6).
Accordingly, we affirm the rejection of claim 10 under 35 U.S.C.
§ 103(a) as unpatentable over the combination of First and MERCK.
However, because our rationale differs from the Examiner’s we affirm this
rejection as a new ground of rejection. 37 C.F.R. § 41.50(b).

Claim 12:
Claim 12 is drawn to a method for treating classic type 1
hypersensitivity comprising the step of administrating a botulinum toxin to
an affected area of a subject suffering from classic type 1 hypersensitivity,
thereby reducing inflammation, wherein the hypersensitivity is hay fever,
rhinitis, allergic rhinitis, allergic forms of eczema, urticaria, rheumatoid
arthritis, inflammatory bowel disease, or asthma.
According to Appellant, the combination of First and MERCK fails to
teach “‘hay fever,’ ‘allergic forms of eczema,’ ‘urticaria,’ or ‘inflammatory
bowel disease’” (App. Br. 19). In this regard, Appellant asserts that
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“[s]hould the Office maintain the instant rejection, Applicant respectfully
requests that the Office specifically indicate where in the references cited in
the rejection these teachings appear” (id.). We decline Appellant’s request.
Claim 12 is not limited to hay fever, allergic forms of eczema, urticaria, or
inflammatory bowel disease. To the contrary, the Markush grouping set
forth in claim 12 includes asthma.
A claimed invention is obvious “if the differences between the subject
matter sought to be patented and the prior art are such that the subject matter
as a whole would have been obvious at the time the invention was made to a
person having ordinary skill in the art to which said subject matter pertains.”
35 U.S.C. § 103(a). To make this determination, we consider, in the context
of the knowledge and level of skill possessed by a person of ordinary skill in
the art, whether such a person would have had reason to combine the prior
art in the fashion claimed by the application at issue. See KSR, 127 S. Ct. at
1740-41. As discussed above, the combination of First and MERCK teach
that asthma is a Type I hypersensitivity reaction that falls within the genus
of neurogenic inflammation that is treatable by the administration of
botulinum toxin. Accordingly, we find that the preponderance of the
evidence on this record supports a conclusion that the claimed method would
have been prima facie obvious to a person of ordinary skill in the art at the
time the invention was made. For the foregoing reasons, we are not
persuaded by Appellant’s assertion to the contrary (App. Br. 19-20) or
Appellant’s assertion that KSR is inapplicable to the facts on this record
(Reply Br. 6).

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Accordingly, we affirm the rejection of claim 12 under 35 U.S.C.
§ 103(a) as unpatentable over the combination of First and MERCK. Claim
11 falls together with claim 12. However, because our rationale differs from
the Examiner’s we affirm this rejection as a new ground of rejection. 37
C.F.R. § 41.50(b).

CONCLUSION
In summary, we reverse the rejections under the enablement and
written description provisions of 35 U.S.C. § 112, first paragraph.
We affirm the rejection of claims 10-12 under 35 U.S.C. § 103(a) as
unpatentable over the combination of First and MERCK. However, because
our rationale differs from that of the Examiner we affirm the rejection as a
new ground of rejection. 37 C.F.R. § 41.50(b).

TIME PERIOD FOR RESPONSE
This decision contains a new ground of rejection pursuant to 37
C.F.R. § 41.50(b) (effective September 13, 2004, 69 Fed. Reg. 49960
(August 12, 2004), 1286 Off. Gaz. Pat. Office 21 (September 7, 2004)). 37
C.F.R. § 41.50(b) provides “[a] new ground 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 appellant, WITHIN TWO
MONTHS FROM THE DATE OF THE DECISION, must exercise one of the
following two options with respect to the new ground of rejection to avoid
termination of the appeal as to the rejected claims:
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(1) Reopen prosecution. 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. . . .

(2) Request rehearing. Request that the proceeding be
reheard under § 41.52 by the Board upon the same record. . . .

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

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