Ex Parte Brusilow

Board of Patent Appeals and Interferences

May 16, 2011

10758415 (B.P.A.I. May. 16, 2011)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte WILLIAM S. BRUSILOW
__________

Appeal 2011-001751
Application 10/758,415
Technology Center 1600
__________

Before ERIC GRIMES, JEFFREY N. FREDMAN, and
STEPHEN WALSH, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
for treating a polyglutamine disease. The Examiner rejected the claims as
obvious. We have jurisdiction under 35 U.S.C. § 6(b). We reverse.

Statement of the Case
Background
“There are a number of neurodegenerative polyglutamine diseases, for
example Huntington‟s disease . . . which are characterized by expanded
genomic CAG sequences resulting in the synthesis and accumulation of
polyglutamine tracts in brain proteins of unknown function” (Spec. 1, ll. 16-
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20). The Specification teaches “a treatment for polyglutamine disorders
caused by expanded genomic CAG nucleotides by reducing the availability
of free glutamine in astrocytes . . . by the administration of effective
amounts of L-methionine S-sulfoximine, L-ethionine S-sulfoximine,
glufosinate and/or branched chain -keto acids” (Spec. 7, ll. 4-12).
The Claims
Claims 1-5, 10, 11, and 21 are on appeal.
1
Claim 1 is representative.
Claim 1 reads as follows:
1. A method for treating a polyglutamine disease,
comprising administering a compound selected from the
group consisting of L-methionine S-sulfoximine, L-
ethionine S- sulfoximine, glufosinate and branched chain -
keto acids derived from leucine, isoleucine or valine, to a
patient in need of such treatment.

The issue
The Examiner rejected claims 1-5, 10, 11, and 21 under 35 U.S.C. §
103(a) as obvious over Apostolakis,
2
Ginefri-Gayet,
3
Liedtke,
4
and
Feurerstein
5
(Ans. 3-5).

1
Claims 6-9 and 12-20 are withdrawn (see App. Br. 2).
2
Apostolakis et al., Long-Term Effects of the Administration of the
Convulsive Substance DL-Methionine-DL-Sulfoximine to the
Rabbit, 23 BRAIN RESEARCH BULLETIN 257-262 (1989).
3
Ginefri-Gayet et al., Possible Link Between Brain Serotonin
Metabolism and Methionine Sulfoximine-Induced Hypothermia
and Associated Behavior in the Rat, 43 PHARMACOLOGY
BIOCHEMISTRY BEHAVIOR 173-179 (1992).
4
Liedtke et al., US 2003/0013650 A1, published Jan. 16, 2003.
5
Feurerstein et al., US 2002/0173537 A1, published Nov. 21,
2002.
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The Examiner finds that “Apostolakis teaches methionine sulfoximine
(MSO) is a centrally acting neurotoxin with convulsive properties; it has
been used in study of epilepsy. MSO suppresses the formation of glutamine”
(Ans. 3). The Examiner finds that “Ginefri-Gayet teaches pharmaceutical
unit doses in an amount of methionine sulfoxim[in]e of 50-75 micro gram/10
micro liters” (id.). The Examiner finds that “Liedtke teaches that the present
invention relates to the identification in vertebrate animals including
humans, of an ion channel for rapid conduction of cations” (id.). The
Examiner finds that “Feurerstein et al. teach of a compound treating
neurodegenerative diseases including polyglutamine diseases (see page 1,
paragraph 0003). The composition is useful for treating a polyglutamine
disease e.g. Huntington‟s disease” (id. at 4).
The Examiner finds that “[c]learly, the skilled artisan is provided with
ample instruction and motivation to use MSO in the treatment of
neurodegenerative diseases including polyglutamine diseases” (id. at 4-5).
Appellant contends that “though Apostolakis indicates that MSO
suppresses the formation of glutamine and glutamate, Apostolakis also
discloses that MSO is a centrally acting neurotoxin with convulsive
properties” (App. Br. 6). Appellant contends that “Apostolakis uses MSO to
induce seizures in order to investigate „a possible correlation of the
probability of occurrence of a seizure with the power spectrum
characteristics of the interictal EEG in the rabbit‟ (page 257, left column)”
(id.). Appellant contends that “Apostolakis concludes that administration of
MSO to rabbits in addition to the known convulsive effects may also be
responsible for hind leg myopathy. Therefore, Apostolakis explicitly teaches
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away from using MSO as a therapeutic treatment for any diseases” (App. Br.
7).
Appellant contends that “Feurerstein is directed to a method for
treating a polyglutamine disorder using 2- pyrrolidinone derivatives.
Feurerstein does not teach the use of MSO and thus does not cure the
deficiencies in Apostolakis, Ginefri-Gayet and Liedtke as discussed above”
(id. at 9).
The issue with respect to this rejection is: Does the evidence of record
support the Examiner‟s conclusion that the combination of Apostolakis,
Ginefri-Gayet, Liedtke, and Feurerstein renders obvious the treatment
method of claim 1?
Findings of Fact
The following findings of fact (“FF”) are supported by a
preponderance of the evidence of record.
1. Feurerstein teaches that “Huntington‟s disease (HD) is also
associated with extracellular glutamate levels. . . . [I]t is caused by a CAG
repeat expansion, corresponding to an elongated polyglutamine segment on
the protein level” (Feurerstein, col. 1 ¶ 0003).
2. Feurerstein teaches that “[s]ubstances which prevent the
excitotoxicity of and the plastic changes due to Glu by reducing the
extracellular Glu level would be a crucial advantage for the therapy and
prophylaxis of the pathological states” (Feurerstein, col. 1 ¶ 0004).
3. Apostolakis teaches that “METHIONINE sulfoximine (MSO)
is a centrally acting neurotoxin with convulsive properties; it has been used
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for a long time as a tool for the experimental study of epilepsy” (Apostolakis
257, col. 1).
4. Apostolakis teaches that “MSO suppresses the formation of
glutamine and glutamate and it has been claimed to reduce the releasable
pool of glutamate, aspartate and GABA” (Apostolakis 257, col. 1).
5. Apostolakis teaches that “[f]ollowing the IV MSO
administration the animals became hyperactive and exhibited increased hind
leg muscle tonus at 2 hr; at 4-5 hr tetanus-like seizures started” (Apostolakis
259, col. 1).
6. Apostolakis teaches that the “seizures were suppressed by high
doses of diazepam . . . Two out of the 14 animals included in our
observations . . . recovered fully by the 4th day, while the condition of the
rest deteriorated further and finally lower limb rigid paralysis set in”
(Apostolakis 259, col. 1-2).
7. Apostolakis teaches that “administration of small doses of MSO
to rabbits, except for their already known convulsive effects, may also be
responsible for hind leg myopathy” (Apostolakis 260, col. 2 to 261, col. 1).
8. Ginefri-Gayet teaches that the “convulsant molecule L-
methionine-D,L-sulfoximine (MSO) intraperitoneally or
intracerebroventricularly administered induced a decrease of body
temperature in the restrained rat” (Ginefri-Gayet 173, col. 1).
9. Ginefri-Gayet teaches that “MSO administered at a convulsant
dose elicited a time-dependent regional perturbation of 5-HT metabolism in
the rodent brain” (Ginefri-Gayet 177, col. 1).
.
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10. Liedtke teaches an ion channel which “demonstrates activity as
an osmoreceptor, and also demonstrates a role in mechanical stimulation and
responsiveness” (Liedtke 1 0002).
Principles of Law
“„[R]ejections on obviousness grounds cannot be sustained by mere
conclusory statements; instead, there must be some articulated reasoning
with some rational underpinning to support the legal conclusion of
obviousness.”‟ KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007).
A reference may be said to teach away when a person of
ordinary skill, upon reading the reference, would be
discouraged from following the path set out in the reference,
or would be led in a direction divergent from the path that
was taken by the applicant. The degree of teaching away
will of course depend on the particular facts; in general, a
reference will teach away if it suggests that the line of
development flowing from the reference's disclosure is
unlikely to be productive of the result sought by the
applicant.

In re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994).
Analysis
Feurerstein teaches treatment of Huntington‟s disease using
substances which reduce extracellular Glutamate levels (FF 1-2), Feurerstein
provides no teaching or suggestion of the specific compounds of claim 1.
Apostolakis and Ginefri-Gayet teach the use of methionine
sulfoximine (MSO), and Apostolakis teaches that MSO reduces the
releasable pool of glutamate (FF 3-9).
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The Examiner does not identify, and we do not find, any reason other
than the common ability to reduce extracellular glutamate levels, which links
these references together.
We agree with Appellant that Apostolakis and Ginefri-Gayet teach
away from the claimed invention (see App. Br. 6). There is no suggestion in
Apostolakis or Ginefri-Gayet to use MSO in any sort of beneficial treatment
whatsoever. There are express teachings in Apostolakis that MSO is a
neurotoxin which induces epilepsy (FF 3), hyperactivity and tetanus like
seizures (FF 5), and hind leg myopathy (FF 7). Ginefri-Gayet teaches that
MSO causes hypothermia (FF 8) and convulsions (FF9).
While side effects alone would not necessarily represent a teaching
away, the instant references teach nothing but negative effects of the
administration of MSO (FF 3-9). There is no reference which teaches or
suggests that MSO would have any positive therapeutic effect whatsoever.
We find the Examiner‟s argument that “if MSO administration causes
undesired side effects, it will necessarily cause the same undesired effects in
Appellant‟s treatment of poly glutamine disease” particularly unpersuasive.
This argument confuses the issues. The issue is not whether MSO will
inherently result in particular side effects, a result which is likely to be dose
dependent. The issue is whether in light of references which teach only side
effects and which do not suggest any therapeutic use for MSO, would the
ordinary artisan have had any reason to apply MSO to a therapeutic use?
Clearly, we find that no prima facie case of obviousness has been
established.
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The Examiner also mischaracterizes Apostolakis, when stating that
“the prior art teaches that at lower concentration there has been some benefit
of using MSO” (Ans. 7). Apostolakis treated 14 animals, with no previously
identified disease, with MSO (see Apostolakis 257, col. 1-2). The 2 animals
which recovered after MSO treatment were subjected to seizures and were
simply shown to have recovered from the negative effects of the MSO
treatment, not to have received any positive or therapeutic effect (see
Apostolakis 259, col. 1-2). We do not consider treatment of healthy animals
with a neurotoxin to constitute a benefit to those animals, even to those
which recover.
Conclusion of Law
The evidence of record does not support the Examiner‟s conclusion
that the combination of Apostolakis, Ginefri-Gayet, Liedtke, and Feurerstein
renders obvious the treatment method of claim 1.
SUMMARY
In summary, we reverse the rejection of claims 1-5, 10, 11, and 21
under 35 U.S.C. § 103(a) as obvious over Apostolakis, Ginefri-Gayet,
Liedtke, and Feurerstein.

REVERSED

JNF

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