Ex Parte Morishita

Board of Patent Appeals and Interferences

Mar 23, 2010

10495132 (B.P.A.I. Mar. 23, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte RYUICHI MORISHITA
__________

Appeal 2009-0095621
Application 10/495,132
Technology Center 1600
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Decided: March 23, 2010
__________

Before ERIC GRIMES, JEFFREY N. FREDMAN, 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 reducing cell death by administering a vector expressing
hepatocyte growth factor (HGF). The Patent Examiner rejected the claims
for lack of enablement. We have jurisdiction under 35 U.S.C. § 6(b). We
reverse.

1 Oral Hearing March 18, 2010.
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STATEMENT OF THE CASE
Claims 26-37, which are all the pending claims, are on appeal. Claim
26 is representative and reads as follows:
26. A method of reducing dopaminergic cell death, comprising
administering directly to the striate body of a subject in need thereof a
pharmacologically effective amount of an expression vector which
encodes and expresses hepatocyte growth factor (HGF), whereby
dopaminergic cell death is reduced.

The Examiner rejected the claims under 35 U.S.C. § 112, first
paragraph as failing to comply with the enablement requirement.

ENABLEMENT
The Issue
The Examiner interpreted the claims to include “treatment” of
Parkinson’s Disease (PD). (Ans. 7.) The Examiner then conducted an
enablement analysis based on the interpretation that the claims are “required
to be enabled for the treatment of Parkinson’s disease, and not just any cell
death.” (Ans. 7-8.)
The Examiner found that the Specification’s first example
“demonstrates that HGF-encoding plasmids, administered to the striate
bodies in rats by direct injection, provide a protective effect against 6-
OHDA-induced cell death when the 6-OHDA is administered 5-days after
gene transfer.” (Id. at 9.) The Examiner also found that Schober2
demonstrated that the 6-OHDA animal model “is not considered by the
Artisan to be a good predictor for therapies which prevent the death of the

2 Andreas Schober, Classic toxin-induced animal models of Parkinson’s
disease: 6-OHDA and MPTP, 318 CELL TISSUE RES. 215-224 (2004).
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neurons themselves.” (Id. at 10.) The Examiner also found that Kahle3
taught that the animal model “does not demonstrate the typical PD
neuropathology.” (Id.) Based on Schober and Kahle, the Examiner found
the understanding in the art was that “Appellant’s model was not reasonably
predictive of treatment of Parkinson’s disease for chemicals which prevent
the dopaminergic cell death.” (Id. at 11.) The Examiner similarly found that
“the Prior Art did not have reasoned basis to link HGF to Parkinson’s
disease such that it could be reasonably predicted that HGF would prevent
cell death of the neurons in the striate body in Parkinson’s disease.” (Id.)
Based on those findings, the Examiner concluded that undue
experimentation would be required to use Appellant’s method, and
concluded that the claims were not enabled. (Id. at 12.)
Appellant contends that the Examiner’s analysis is based on a
mischaracterization of the claimed method and the description of the
invention in the Specification. (App. Br. 3.)
Appellant contends that the Morishita Declaration shows that at the
time the application was filed, the 6-OHDA model “was accepted in the art
as a valid model for identifying and testing neuroprotective treatments for
PD.” (Id. at 6.) The Ishida Declaration is said to evidence “the wide
acceptance of neurotoxin-induced animal models of PD,” and that “6-OHDA
models have successfully demonstrated neuroprotective effects of many
compounds.” (Id. at 7.)

3 Philipp J. Kahle et al., The emerging utility of animal models of chronic
neurodegenerative diseases, 5 EMERGING THERAPEUTIC TARGETS 125-132
(2001).
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In response to the Examiner’s assessment of predictability in this art,
Appellant contends that the evidence demonstrates that “HGF is reliably
expressed at sufficient levels to reduce dopaminergic cell death.” (Id. at 7.)
Appellant argues that the evidence on the other Wands factors favors a
conclusion of enablement for the method of reducing dopaminergic cell
death. (Id. at 7-10.)
The issue with respect to this appeal is whether the evidence of record
weighs in favor of enablement.

Findings of Fact
Specification
1. The Specification discloses “Example 1,” which demonstrated that an
expression vector encoding HGF reduced dopaminergic cell death
when administered to rats in a 6-OHDA rat model. (Spec. 21-24.)
Declaration Under 37 C.F.R. § 1.132, Ryuichi Morishita, Mar. 26, 2007
(“First Morishita Decl.”)
2. Declarant states that “[d]estruction of dopamine neurons using 6-
OHDA has been used to create animal models of Parkinson’s disease
for many years (‘6-OHDA model’) and has been used to screen and to
study potential neuroprotective agents.” (First Morishita Decl. ¶ 7,
citing Exhibits 3-15.)
3. Declarant states that “[a] neuroprotective effect was shown in each of
Exhibits 3-15” (¶9) “before the Nov. 28, 2001 priority date of this
application” (¶8).
4. Declarant states that many of the neuroprotective agents selected for
investigation in clinical trials for treating Parkinson’s disease were
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identified in animal models, including the 6-OHDA model. (First
Morishita Decl. ¶ 7, citing Exhibits 3-15.)
Declaration Under 37 C.F.R. § 1.132, Ryuichi Morishita, Oct. 30, 2007
(“Second Morishita Decl.”)
5. Declarant states that in a nonhuman primate model of Parkinson’s
disease, “injection of a plasmid encoding human hepatocyte growth
factor (HGF) into the striatum protected the dopaminergic neurons
from the toxicity induced by 1-methyl-4-phenyl-1,2,3,6-
tetrahydropyridine (MPTP).” (Second Morishita Decl. ¶4.)
6. Declarant states that MPTP treatment mimics the onset of PD.
(Second Morishita Decl. ¶14.)
Declaration of Dr. Akihiko Ishida Under 37 C.F.R. § 1.132 (“Ishida Decl.”)
7. Declarant states that “[a]nimal models of PD obtained by treating
animals with certain neurotoxins are well accepted in the art as
experimental models of PD.” (Ishida Decl. ¶4.)
8. Declarant cites the Bové review4 for its statement that “‘the monkey
MPTP model remains the gold standard for the assessment of novel
strategies and agents for the treatment of PD symptoms.’ Bové at
page 488 ¶ 1.” (Ishida Decl. ¶6.)
9. Declarant cites evidence said to show that “[a]nimal models of PD
created using 6-OHDA and MPTP . . . have been and still are used to
test a variety of therapies ranging from neurosurgical lesions to gene
therapy” et al. (Ishida Decl. ¶7, citations omitted.)

4 Jordi Bové et al., Toxin-Induced Models of Parkinson’s Disease,
2 NEURORX® 484-494 (2005).
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10. Declarant cites evidence said to show that at least 10 agents tested in
the 6-OHDA or MPTP model have become approved drugs for
treating Parkinson’s disease. (Ishida Decl. ¶¶8- 18, citations omitted.)

Principles of Law
The first paragraph of 35 U.S.C. § 112 requires that the specification
teach persons skilled in the art to use the invention without undue
experimentation. In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988). The
disclosure must provide sufficient guidance to enable those of skill in the art
to use the invention as broadly as claimed. In re Vaeck, 947 F.2d 488, 496
(Fed. Cir. 1991). Assuming there is sufficient reason to think undue
experimentation would be needed to use an invention, a rejection for failure
to teach how to use would be proper. In re Marzocchi, 439 F.2d 220, 223
(CCPA 1971).

Analysis
The evidence supports Appellant’s argument that the 6-OHDA animal
model was used before the filing date in selecting drugs for Parkinson’s
disease clinical trials. (FF2 and 4.) Appellant provided evidence that the
claimed method works in the rat 6-OHDA model. (FF1.) Appellant also
provided evidence that the claimed method works in a primate MPTP model.
(FF5.) The evidence supports Appellant’s argument that the MPTP model
was used before the filing date in selecting drugs for Parkinson’s disease
clinical trials. (FF10.) We agree with Appellant that the record evidence
does not support concluding that undue experimentation would be required
to use the claimed method of reducing dopaminergic cell death.
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CONCLUSION
The evidence of record weighs against a conclusion of non-
enablement.
SUMMARY
We reverse the rejection of claims 26-37 under 35 U.S.C. § 112, first
paragraph as failing to comply with the enablement requirement

REVERSED

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