Ex parte Skolnick et al.

Board of Patent Appeals and Interferences

Sep 22, 1998

07390745 (B.P.A.I. Sep. 22, 1998)

Application for patent filed August 8, 1989. 1
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THIS OPINION WAS NOT WRITTEN FOR PUBLICATION
The opinion in support of the decision being entered today
(1) was not written for publication in a law journal and
(2) is not binding precedent of the Board.
Paper No. 53
UNITED STATES PATENT AND TRADEMARK OFFICE
____________
BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
____________
Ex parte PHIL SKOLNICK, ANITA LEWIN,
JUAN-CARLOS MARVIZON, JAMES MONN, and KENNER RICE
____________
Appeal No. 97-1999
Application 07/390,7451
____________
Oral Hearing: August 7, 1997
____________
Before METZ, GRON, and ELLIS, Administrative Patent Judges.
GRON, Administrative Patent Judge.
DECISION ON APPEAL UNDER 35 U.S.C. § 134
This is an appeal under 35 U.S.C. § 134 from an
examiner’s decision to reject the patentability of Claims 1-
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21, all claims pending in this application.
1. Introduction
Claims 15-21 stand rejected under 35 U.S.C. § 102(b) as
fully described by Schröder et al. (Schroder), U.S. 4,554,017,
patented November 19, 1985. Claims 1-21 stand rejected under
35 U.S.C. § 103 as being unpatentable in view of the combined
teachings of Nadler et al. (Nadler), “1-Aminocyclopropane-1-
Carboxylic Acid (ACC) Mimics the Effects of Glycine on the
NMDA Receptor Ion Channel,” European Journal of Pharmacology,
Vol. 157, pp. 115-116 (November 1988)(prima facie prior art
under
35 U.S.C. § 102(a)); Marvizón, Lewin, and Skolnick (Marvizon),
“1-Aminocyclopropane Carboxylic Acid: A Potent and Selective
Ligand for the Glycine Modulatory Site of the N-Methyl-D-
Aspartate Receptor Complex,” Journal of Neurochemistry, Vol.
52, No. 3, pp. 992-994 (March 1989)(prima facie prior art
under
35 U.S.C. § 102(a)); Chemical Abstracts (Ross), Vol. 85, No.
4,
AB-743, Abstract No. 39814 (1987); Robinson et al. (Robinson),
“Glutamate and Related Acidic Excitatory Neurotransmitters:
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From Basic Science to Clinical Application,” FASEB Journal,
Vol. 1, No. 6, pp. 446-455 (1987); and Foster et al. (Foster),
“Taking Apart NMDA Receptors,” Nature, Vol. 329, pp. 395-396
(1987).
Claims 1-5 and 15 are representative of the subject
matter claimed and read:
1. A method of treating a
neuropsychopharmacological
disorder in a patient, wherein the neuropsychopharmaco-
logical disorder treated results from or is associated
with excessive activation of the N-methyl-D-aspartate
[(NMDA)] receptor complex, said method comprising:
administering to a patient in need of treatment
thereof a compound possessing partial agonist properties
for the strychnine insensitive glycine modulatory site of
the N-methyl-D-aspartate receptor complex in an amount
effective to alleviate the symptoms of the neuropsycho-
pharmacological disorder.
2. The method of claim 1), wherein the neuropsycho-
pharmacological disorder treated is selected from:
epilepsy, stroke, anxiety, Alzheimer’s disease,
Parkinson’s Disease, Guam ALS, dementia, and lathyrism.
3. The method of claim 1, wherein the neuropsycho-
pharmacological disorder is an epilepsy or anxiety
disorder.
4. The method of claim 1, wherein the disorder is
an epilepsy disorder.
5. The method of claim 1, wherein said compound has
the formula:
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A C=O
\ / \
C B Formula I
/ \
C - C
wherein A is -NH , -NHR or -NR R ; B is -OH or -OR ; 2 1 1 2 3
R , R and R , same or different, are selected from lower1 2 3
alkyl, which may be substituted by halogen, hydroxyl,
lower alkoxy, oxo, mercapto, aryl or amino; or a
pharmaceutically acceptable salt thereof.
15. A pharmaceutical composition for the treatment
of a neuropsychopharmacological disorder which results
from or is associated with excessive activation of the
N-methyl-D-aspartate receptor complex, comprising:
(a) a compound having the formula:
A C=O
\ / \
C B Formula I
/ \
C - C
wherein A is -NH , -NHR or -NR R ; B is -OH or -OR ; 2 1 1 2 3
R , R and R , same or different, are selected from lower1 2 3
alkyl, which may be substituted by halogen, hydroxyl,
alkoxy, oxo, mercapto, aryl or amino; or a
pharmaceutically acceptable salt thereof; and
(b) a pharmaceutically acceptable carrier thereof
suitable for administration to a patient, wherein when
the
carrier is water, the carrier further includes isotonic
agents.
2. Discussion
A. The section 102 rejection
We reverse the examiner’s rejection of Claims 15-21 under
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35 U.S.C. § 102(b) because the claimed compositions are not
fully described by Schroder. During the examination process,
the language of the claims is to be given its broadest
reasonable interpretation consistent with the description of
the invention in the specification. In re Zletz, 893 F.2d
319, 321, 13 USPQ2d 1320, 1322 (Fed. Cir. 1989). In that
light, the compositions appellants claim must be interpreted
to include only those pharmaceutical compositions which are
suitable “for administration to a patient” (Claim 15), i.e.,
“suitable pharmaceutical formulations for administering by
injection” (Specification, p. 12, l. 22-24). The
specification teaches (1)(Specification, p. 26, l. 2-8):
The Formula I partial agonist compounds of the
present invention may be made into sterile pharmaceutical
compositions for injection, by combination with
appropriate
pharmaceutically acceptable carriers or diluents, and may
be formulated into preparations in liquid for injections
in the usual ways for this respective route of
administration.
(2)(Specification, p. 27, l. 9-12):
Parenteral administration of the compounds of the
present invention can easily be had by a pharmaceutically
acceptable carrier, such as Sterile Water for Injection,
USP, or by a sterile saline solution.
and (3) (Specification, p. 28, l. 8-10):
Possible routes of administration include
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intravenous
(i.v.), subcutaneous (s.c.), intramuscular (i.m.) and
intraperitoneal (i.p.).
While Schroder certainly describes compositions
comprising 1-aminocyclopropane carboxylic acid or its lower
alkyl esters in water (Schroder, col. 12, l. 29-58), with the
possible inclusion of “salts of iron, manganese, boron,
copper, cobalt, molybdenum and zinc” (Schroder, col. 13, l.
20-25), the compositions are taught to be useful for
application to plants to regulate plant growth (Schroder, col.
21, Claim 1). While we agree with the examiner that
Schroder’s compositions for application to plants to regulate
growth may be sterile and may contain pharmaceutical grade
carriers and pharmaceutically acceptable salts in amounts
suitable for human injection, we find in Schroder no
description of the pharmaceutical compositions appellants
claim which would have reasonably placed that subject matter
in the possession of the public. Accordingly, we reverse the
examiner’s rejection of Claims 15-21 under 35 U.S.C. § 102(b)
as anticipated by Schroder.
B. The Section 103 rejection
Appellants do not appear to contest the examiner’s
finding that the combined teachings of Ross, Robinson, and
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Foster would have led persons having ordinary skill in the art
to understand that the NMDA receptor complex is associated
with neuropsycho-pharmacological disorders such as epilepsy,
stroke, anxiety, Alzheimer’s disease, Parkinson’s Disease,
Guam ALS, dementia, and lathyrism. Rather, appellants argue
(1) that neither Nadler nor Marvizon is prior art under 35
U.S.C. § 102(a), and (2) the combined teachings of Nadler and
Marvizon reasonably would not have led persons having ordinary
skill in the art to make and use the invention appellants
claim with reasonable expectation of successfully treating
neuropsychopharmacological disorders associated with excessive
activation of the NMDA receptor complex (Appeal Brief, pp. 11-
14).
In support of argument (1), appellants filed two
declarations. The first is a Declaration Under 37 CFR 1.132
by Phil Skolnick which is supported by an article by Skolnick,
Marvizon, Jackson, Monn, Rice, and Lewin (Skolnick), “Blockade
of N-Methyl-D-Aspartate Induced Convulsions by 1-
Aminocyclopropane- carboxylates,” Life Sciences, Vol. 45, No.
18, pp. 1647-1655 (1989)(Paper No. 8, filed February 19,
1991). In part VI of that declaration, Skolnick declares
(Skolnick Rule 132 declaration,
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p. 3, part VI):
[E]ven though the [Marvizon and Skolnick] references
. . . name co-authors different from the named co-
inventors on the present application, the disclosures
therein of portions of the present invention are made
by the present inventors.
Given that declaration, In re Katz, 687 F.2d 450, 454, 215
USPQ 14, 17 (CCPA 1982), instructs:
[O]ne’s own work is not prior art under § 102(a) even
though it has been disclosed to the public in a manner
or form which otherwise would fall under § 102(a).
Disclosure to the public of one’s own work constitutes
a bar to the grant of a patent claiming the subject
matter so disclosed (or subject matter obvious therefrom)
only when the disclosure occurred more than one year
prior
to the date of the application . . . .
However, Skolnick also declares (Skolnick Rule 132
declaration, p. 2, part III):
That disclosures contained in the [Marvizon] reference
. . . are made by the present co-inventors Marvizon,
Lewin
and myself and relate to the use of 1-aminocyclopropane-
carboxylic acid in the present invention. That since my
co-inventors James Monn and Kenner Rice contribution to
the present invention dealt with the synthesis and use of
ester derivatives of 1-aminocyclopropanecarboxylic acid
in the present invention; and since this portion of the
present invention was not disclosed in the [Marvizon]
reference . . . co-inventors James Monn and Kenner Rice
were excluded as authors of the reference . . . .
Skolnick’s declaration does not establish what if any of
the subject matter disclosed in the Marvizon reference, which
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relates to the disclosed use of and uses for 1-
aminocyclopropane carboxylic acid taught in this application,
was made by Marvizon, Lewin, Skolnick, Monn and Rice rather
than Marvizon, Lewin, and Skolnick. Skolnick’s declaration
strongly suggests that all subject matter disclosed in this
application which relates to the use of the esters of 1-
aminocyclopropanecarboxylic acid was made by Marvizon, Lewin,
Skolnick, Monn, and Rice. However, Skolnick does not explain
why his declaration appears to be inconsistent with the
original declaration which supports the present application.
That declaration indicates that Marvizon, Lewin, Skolnick,
Monn, and Rice are the inventors of all the subject matter
defined by the claims on appeal as a whole. We find that
Skolnick’s Rule 132 declaration is confusing at best and does
not satisfactorily explain what subject matter disclosed in
Marvizon was invented by Marvizon, Lewin, Skolnick, Monn, and
Rice, the named inventive entity of this case, and cannot
therefore be considered prior art under 35 U.S.C. § 102(a) as
to the subject matter of the claims here on appeal. On the
face of Marvizon, all the subject matter the reference
discloses appears to be prior art under 35 U.S.C. § 102(a).
Skolnick’s Rule 132 declaration does not satisfactorily
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explain why Marvizon may not be considered prior art under §
102(a).
A Declaration under 37 CFR § 1.131 by Skolnick, Lewin,
Marvizon, Monn, and Rice filed on March 20, 1995 (Paper No.
31) reads on page 2, paragraphs 3 and 4, thereof:
3. At least as early as November 15, 1988, ethyl
and methyl esters of ACPC were conceived, synthesized and
tested for activity by three of us, Phil Skolnick, James
Monn, and Kenner Rice, prior to publication of the
Marvisón [sic, Marvizón], et al., and Nadler, et al.
publications, as demonstrated by Attachment A.
Attachment A are notebook pages, from the laboratory manual
of Barrington Jackson, a student who conducted research
in Dr. Skolnick’s laboratory at his direction and under his
supervision, with dates marked out.
4. At least as early as November 15, 1988, ACPC had
been conceived, obtained and tested for binding to the
glycine site of the NMDA receptor, by Phil Skolnick,
Anita Lewin, and Juan-Carlos Marvizon, as demonstrated by
Attachment B. Attachment B are pages from the laboratory
manual of Dr. Marvisón [sic, Marvizón], with the dates
marked out.
The declarants support the above statements with Attachments A
and B which appear to be copies of laboratory notebook pages
and a computer-originated data sheet. The purpose, content,
and meaning of the information in the attached laboratory
notebook pages and data sheets are unclear from the attached
papers themselves. Moreover, the declarants proffer no
further explanation of that information in the text of the
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declaration which refers to the attachments' information.
Declarants do conclude and argue in simultaneously filed
papers and their later briefs on appeal, that the attached
evidence supports a conclusion that Skolnick, Lewin, Marvizon,
Monn, and Rice conceived of and/or reduced to practice the
subject matter of the claims on appeal at least as early as
November 15, 1988 (Appeal Brief, p. 12). We fail to see how
the unclear and unexplained information displayed by the
papers supports declarants’ conclusion that applicants
conceived, synthesized and tested ACPC or its ethyl and methyl
esters for activity in treating neuropsycho-pharmacological
disorders by administration to a patient and/or conceived,
obtained and tested pharmaceutical compositions comprising
ACPC or its ethyl and methyl esters and a pharmaceutically
acceptable carrier thereof suitable for administration to a
patient for binding to the glycine site of the NMDA receptor,
at least as early as November 15, 1988.
While we might speculate as to the meaning of the attachments
and what they may or may not indicate, we find that
speculation is poor support for patentability and will not do
so. Accordingly, appellants have not rebutted our holding
that everything Nadler and Marvizon disclose prima facie is
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prior art under 35 U.S.C.
§ 102(a).
We nevertheless reverse the examiner’s holding that
Claims 1-21 are unpatentable under 35 U.S.C. § 103 in view of
the combined teachings of Nadler, Marvizon, Ross, Robinson,
and Foster. In our view, persons having ordinary skill in the
art would not have been led by the combined teachings to
expect success in treating neuropsychopharmacological
disorders with pharmaceutical compositions comprising ACPC or
its esters. We find that the applied prior art would not have
enabled one skilled in the art to treat
neuropsychopharmacological disorders by injection of
pharmaceutically acceptable compositions of ACPC or its esters
with reasonable expectation of success without undue further
experimentation, i.e., at best the combined prior art
teachings create an “obvious-to-try” situation. See In re Eli
Lilly & Co., 902 F.2d 943, 945,
14 USPQ2d 1741, 1743 ((Fed. Cir. 1990):
An “obvious-to-try” situation exists when a general
disclosure may pique the scientist’s curiosity, such that
further investigation might be done as a result of the
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disclosure, but the disclosure itself does not contain a
sufficient teaching of how to obtain the desired result,
or that the claimed result would be obtained if certain
directions were pursued.
We find from Nadler’s teaching that compounds which are
glycine agonists or antagonists or compounds which mimic the
effects of glycine on the NMDA receptor in vitro, “might
therefore serve as effective pharmacotherapeutic agents in
abnormal NMDA-receptor functioning, through altering the
efficacy of glutamate at its own sites” (Nadler, p. 115, col.
1, para. 1). Nadler’s results “indicate that ACC, like
glycine, does not act at the glutamate binding site” (Nadler,
p. 116, col. 1). Nadler “found that ACC . . . mimics the
effects of glycine in that it potentiates the NMDA . . .
evoked currents in a concentration-dependent manner” (Nadler,
p. 116, col. 1). However, Nadler’s analysis of his own
results reasonably would not have suggested to persons having
ordinary skill in the art that ACC or its esters could be
effectively used to treat neuropsycho-pharmacological
disorders. To the contrary, Nadler states (Nadler, p. 116,
col. 2):
The contrasting activities of these two amino acids[,
ACC and cycloleucine,] may enable them to serve as models
for current studies being carried out in our laboratory
in an attempt to design new derivatives of greater
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therapeutic potency.
Thus, we agree with appellants’ view that persons having
ordinary skill in the art would have been led by Nadler’s
disclosure to believe that Nadler himself doubted the
therapeutic efficacy of ACC and looked to design new
derivatives of greater therapeutic potency.
Marvizon’s recognition that ACPC, the compound Nadler
labels ACC, “exhibits the characteristics of a potent and
selective partial agonist at these glycine modulatory sites”
(Marvizon,
p. 992, col. 2) does not remedy or supplant the deficiencies
of Nadler. While Marvizon’s findings, like those of Nadler,
strongly suggest that ACPC and glycine “act at a common site
on the NMDA receptor complex” (Marvizon, p. 994, col. 1) and
that “ACPC is a potent and selective ligand of the glycine
modulatory site coupled to NMDA receptors” (Marvizon, p. 994,
final para.), and Marvizon further indicates that “ACPC . . .
seems to behave as a partial agonist at these sites”
(Marvizon, p. 994, final para.), Marvizon, based on no more
evidence than this, merely states that “ACPC may prove useful
in neurochemical, pharmacological, and electrophysiological
studies of the NMDA receptor complex” (Marvizon, p. 994, final
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para., concluding sentence). This, in our view, would not
have suggested the use of ACPC for treating
neuropsychopharmacological disorders. Rather, it is an
invitation to experiment. Thus, we also find, based on this
evidence, that persons having ordinary skill in the art
reasonably could not have expected success using ACPC or its
esters to treat neuropsychopharmacological disorders.
Therefore, even if we assume, arguendo, that the applied prior
art teachings would have suggested the claimed method to
persons having ordinary skill in the art, we find that they
would not have had a reasonable expectation of successfully
treating neuropsychopharmacological disorders using the
compounds described therein. Accordingly, we are obliged to
reverse the examiner’s rejections under 35 U.S.C. § 103 in
view of the combined teachings of Nadler, Marvizon, Ross,
Robinson, and Foster.
3. Other issues
Consistent with the findings and conclusions in our
Discussion, we find from the evidence and arguments of record
that the art to which the subject matter claimed in this case
pertains, is highly unpredictable. We also find that the
specification filed in support of the claims on appeal
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provides substantial evidence in support of claims drawn to
methods of treating neuropsychopharmacological disorders with
pharmaceutical compositions comprising ACPC and its esters.
However, it appears to this panel that Claims 1-4 are not
commensurate in scope with the scope of support in the
specification. Claims 1-4 are directed to methods of treating
neuropsychopharmacological disorders comprising administering
to a patient in need of treatment thereof “a compound
possessing partial agonist properties for the strychnine
insensitive glycine modulatory site of the N-methyl-D-
aspartate receptor complex in an amount effective to alleviate
the symptoms of the neuropsychopharmacological disorder”
(Claim 1). Even with knowledge of their NMDA receptor-
regulating activity, Nadler makes it clear that amino acids of
similar structure have contrasting activities and ACPC
activity might invite persons skilled in the art to “attempt
to design new derivatives of greater therapeutic potency”
(Nadler, p. 116, col. 2, last sentence). It is not clear to
us how the limited number and kind of examples in this
specification, i.e., ACPC and its esters, which in effect are
one example, support broad claims to methods for treating
neuropsychopharmacological disorders generally with any
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compound possessing partial agonist properties for the
strychnine insensitive glycine modulatory site of the N-
methyl-D-aspartate receptor complex in an amount effective to
alleviate the symptoms of any neuropsycho-pharmacological
disorder.
We recognize that In re Marzocchi, 439 F.2d 220, 224,
169 USPQ 367, 369-370 (CCPA 1971), instructs:
[I]t is incumbent upon the Patent Office, whenever a
rejection . . . [under section 112, first paragraph] is
made, to explain why it doubts the truth or accuracy of
any statement in a supporting disclosure and to back
up assertions of its own with acceptable evidence or
reasoning which is inconsistent with the contested
statement.
Nevertheless, Nadler and Marvizon themselves strongly suggest,
and appellants have argued consistent with that suggestion,
that persons having ordinary skill in the art reasonably could
not have predicted success in treating
neuropsychopharmacological disorders with agonists,
antagonists, or partial agonists which are structurally
similar to ones previously found to exhibit moderate success
either in in vitro tests or in vivo tests using model animals.
See pages 8-9 of Transmittal of Art, filed August 19, 1997,
which we invite the examiner to study. In an unpredictable
art, Section 112 requires that the scope of the claimed
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subject matter bear a reasonable correlation to the scope of
enablement provided by the specification. See generally Amgen
Inc. v. Chugai Pharmaceutical Co., 927 F.2d 1200, 1212-1214,
18 USPQ2d 1016, 1026-1028 (Fed. Cir.), cert. denied, 502 U.S.
856 (1991), and In re Fisher, 427 F.2d 833, 836, 839, 166 USPQ
18, 21-22, 24 (CCPA 1970). It appears from the evidence in
this record that the limited teachings in the specification
with only one example of an effective partial agonist, would
not have enabled persons skilled in an art, which was
unpredictable at the time of this invention, to determine
which compounds are partial agonists for the strychnine
insensitive glycine modulatory site of the N-methyl-D-
aspartate receptor complex and predict which of those would
effectively alleviate the symptoms of any
neuropsychopharmacological disorder, without undue
experimentation.
However, in that the examiner, based on much the same
evidence, declined to raise the issue of compliance with the
first paragraph of 35 U.S.C. § 112 either in favor of the
rejection under section 103 or for reasons otherwise unclear
to this panel, we leave the matter of compliance with the
first paragraph of 35 U.S.C. § 112 based on all the evidence
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Including the new evidence and argument in the2
Transmittal of Art filed August 19, 1997.
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now of record for the examiner to determine in the first2
instance. We remand this application to the examiner for that
purpose.
4. Conclusion
We reverse the examiner’s rejection of Claims 15-21 under
35 U.S.C. § 102(b) over Schroder.
We reverse the examiner’s rejection of Claims 1-21 under
35 U.S.C. § 103 as being unpatentable in view of the combined
teachings of Nadler, Marvizon, Ross, Robinson, and Foster.
We remand the application to the examiner for
consideration of the patentability of Claims 1-4 under 35
U.S.C. § 112, first, paragraph, as indicated in the “Other
issues” section of this decision.
This application, by virtue of its "special" status,
requires an immediate action. Manual of Patent Examining
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Procedures § 708.01(d)(6th ed., rev. 3, July 1997). It is
important that the Board be informed promptly of any action
affecting the appeal in this case.
REVERSED; REMANDED
Andrew, H. Metz )
Administrative Patent Judge )
)
)
)
Teddy S. Gron ) BOARD OF
PATENT
Administrative Patent Judge ) APPEALS AND
) INTERFERENCES
)
)
Joan Ellis )
Administrative Patent Judge )
tdc
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Patrea L. Pabst
Arnall Golden & Gregory LLP
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