Ex parte Gross

Board of Patent Appeals and Interferences

Apr 28, 2000

08063067 (B.P.A.I. Apr. 28, 2000)

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for publication in a law journal and (2) is not binding precedent of the Board.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. 48
UNITED STATES PATENT AND TRADEMARK OFFICE
____________
BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
____________
Ex parte STEVEN S. GROSS
____________
Appeal No. 1996-3326
Application No. 08/063,067
____________
HEARD: April 19, 2000
____________
Before KIMLIN, WALTZ, and KRATZ, Administrative Patent Judges.
WALTZ, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 from the
examiner’s final rejection of claims 1 through 12, which are
the only claims in this application.
According to appellant, the invention is directed to two
embodiments. The first embodiment involves the administration
of known groups of tetrahydrobiopterin synthesis antagonists
Appeal No. 1996-3326
Application No. 08/063,067
The examiner has listed #1227 and #7834 from the Merck1
Index as “prior art of record relied upon in the rejection of
claims under appeal” (Answer, page 2). However, we do not
find this reference applied against any claims in any
rejection in the Answer.
2
to subjects under cytokine therapy for the prophylaxis or
treatment of systemic hypotension caused by pathological
overproduction of nitric oxide from arginine in vascular cells
of the subject (Brief, pages 1-2). The second embodiment
involves administration of known groups of tetrahydrobiopterin
synthesis antagonists to subjects for the prophylaxis or
treatment of systemic hypotension caused by pathological
overproduction of nitric oxide from arginine induced in
vascular cells in said subject by bacterial endotoxins (Brief,
page 2). A copy of illustrative claims 1 and 6 is attached as
an Appendix to this decision.
The examiner has relied upon the following references as1
evidence of obviousness:
Austel et al. (Austel) 4,670,438 Jun. 2,
1987
Nichol et al. (Nichol) 4,701,455 Oct. 20,
1987
Spada et al. (Spada) 5,002,944 Mar. 26,
1991
Appeal No. 1996-3326
Application No. 08/063,067
The examiner, on page 2 of the Answer, lists the abstract2
of this article as part of the prior art of record relied upon
in the rejection (“111CA:230525q”) but subsequently employs
the full article as a basis for the § 103 rejection (see the
Supplemental Answer dated Mar. 1, 1995, Paper No. 35).
This reference is listed as prior art on page 2 of the3
Answer under the name “Salverini” while recited as “Salvemin”
in the rejections on pages 3 and 4 of the Answer. For
purposes of this decision, we refer to and cite this reference
under the name recited in Chemical Abstracts, i.e., Salvemini.
The final rejections of claims 1-12 under the first4
paragraph of 35 U.S.C. § 112 and claims 1-12 under 35 U.S.C.
§ 102(b) as anticipated by Rees or Salvemini or Kwon or Spada
or Nichol or Austel have been withdrawn by the examiner on
page 1 of the Supplemental Answer dated Mar. 1, 1995, Paper
No. 35 (see also the Answer, pages 1-2).
3
Ayling et al. (Ayling) 84/04040 Oct. 25,
1984
(Published International Application)
Rees et al. (Rees), Chemical Abstracts, 110:112347q (1989)
Kwon et al. (Kwon), “Reduced Biopterin as a Cofactor in the2
Generation of Nitrogen Oxides by Murine Macrophages,” J. Biol.
Chem., Vol. 264, No. 34, pp. 20496-20501 (Dec. 5, 1989).
Salvemini et al. (Salvemini), Chemical Abstracts, 115:204139e3
(1991).
Claims 1 through 12 stand rejected under 35 U.S.C. § 103
as unpatentable over Rees, Salvemini and Kwon in view of
Ayling, Spada, Nichol and Austel (Answer, page 4). We4
reverse this rejection for reasons which follow.
Appeal No. 1996-3326
Application No. 08/063,067
4
OPINION
“[T]he examiner bears the initial burden, on review of
the prior art or on any other ground, of presenting a prima
facie case of unpatentability.” In re Oetiker, 977 F.2d 1443,
1445, 24 USPQ2d 1443, 1444 (Fed. Cir. 1992). Furthermore, in
construing the scope of the claims, the examiner must give
effect to all claim limitations. See In re Angstadt, 537 F.2d
498, 501, 190 USPQ 214, 217 (CCPA 1976). Therefore the locus
or population of subjects that is treated in the method of the
claims on appeal is limited to those subjects with hypotension
caused by pathological overproduction of nitric oxide from
arginine induced in vascular smooth muscle cells by therapy
with cytokine (claim 1) or by bacterial endotoxins (claim 6).
The examiner finds that the teachings of Kwon “would have
motivated the skilled artisan, charged with treating
hypotension to reduce cellular NO levels by inhibiting the2
activity of dihydrofolate reductase.” (Supplemental Answer,
page 5). However, the examiner has not rebutted appellant’s
argument that Kwon is directed only to the generation of
nitrogen oxides in murine macrophages, not vascular cells (see
Appeal No. 1996-3326
Application No. 08/063,067
5
the Supplemental Reply Brief dated Mar. 24, 1995, page 6).
The examiner has also not answered appellant’s contention that
the data in Kwon shows there is a reservoir of
tetrahydrobiopterin in uninduced macrophages which is greater
than that necessary for producing maximal generation of nitric
oxide, thus leading away from inhibiting the induction of
tetrahydrobiopterin to reduce nitric oxide synthesis
(Supplemental Reply Brief, page 2).
The other primary references to Rees and Salvemini do not
remedy the deficiencies noted above with regard to Kwon. Rees
is directed to the blocking of NO production by L-NMMA while
Salvemini, like Kwon, is directed to macrophages, teaching
that L-NMMA “probably inhibits NO formation from L-arginine.”
(See the Answer, page 5).
The examiner finds that the secondary references to
Spada, Nichol and Austel “teach various pterion analogs and
homologs as useful for treating various cardiac conditions to
include hypotension.” (Answer, page 5). We agree with
appellant (Brief, pages 24-25) that this finding is an
overgeneralization. The compounds of Austel lower blood
pressure (column 12, lines 17-22) which is the opposite effect
Appeal No. 1996-3326
Application No. 08/063,067
6
of the claimed method. The compounds of Nichol may be used to
treat “orthostatic hypotension” and other diseases caused by a
deficiency of catecholamines and serotonin (column 1, lines 6-
16; column 3, lines 1-5; and column 4, lines 55-61). Thus
Nichol is not concerned with hypotension due to cytokine
therapy or bacterial endotoxins. Spada does not disclose
treatment of hypotension but is directed to compounds with
cardiotonic properties (column 1, lines 9-16; lines 35-37;
column 2, lines 45-47; and column 14, lines 40-42).
The examiner finds that Ayling teaches “various methods
by which pterion [sic] cofactors mediate the enzyme systems
responsible for biological nitric oxide production.” (Answer,
page 5). As noted by appellant on page 23 of the Brief,
Ayling is directed to treating conditions stemming from a
deficiency in tetrahydrobiopterin by providing a substitute
and does not suggest blocking its induction (see Ayling, page
16).
For the foregoing reasons, we determine that the
examiner’s conclusion of obviousness is not supported by the
facts. Therefore the examiner has not presented a prima facie
case of obviousness. In view of this determination, we need
Appeal No. 1996-3326
Application No. 08/063,067
7
not reach the issue of the sufficiency of the declaration
evidence (see the Stuehr and Gross Declarations under 37 CFR §
1.132 dated Nov. 15, 1993, attached to Paper No. 22). In re
Geiger, 815 F.2d 686, 688, 2 USPQ2d 1276, 1278 (Fed. Cir.
1987). Accordingly, the rejection of claims 1 through 12
under 35 U.S.C. § 103 is reversed.
The decision of the examiner is reversed.
OTHER ISSUES
Upon the return of this application to the jurisdiction
of the examiner, the examiner and applicant should consider
the patentability of the claims under the judicially created
doctrine of obviousness-type double patenting in light of
recently issued patents to applicant (see at least U.S.
Patents 5,502,050; 5,874,433; 5,877,176; and especially claims
7 and 9 of U.S. Patent No. 5,880,124).
REVERSED
Appeal No. 1996-3326
Application No. 08/063,067
8
EDWARD C. KIMLIN )
Administrative Patent Judge )
)
)
)
) BOARD OF PATENT
THOMAS A. WALTZ ) APPEALS
Administrative Patent Judge ) AND
) INTERFERENCES
)
)
)
PETER F. KRATZ )
Administrative Patent Judge )
lp
Appeal No. 1996-3326
Application No. 08/063,067
9
ERIC S. SPECTOR
JONES, TULLAR & COOPER
P.O. BOX 2266
EADS STATION
ARLINGTON, VA 22202
Appeal No. 1996-3326
Application No. 08/063,067
10
APPENDIX
Claim 1. A method of prophylaxis or treatment of a subject
for systemic hypotension caused by pathological overproduction
of nitric oxide from arginine induced in vascular smooth
muscle cells in said subject by therapy of said subject with a
cytokine, said method comprising administering to said subject
of a therapeutically effective amount of (a) at least one
guanosine triphosphate pathway tetrahydrobiopterin synthesis
antagonist which is not a reduced pterin that is a substrate
for the pterin salvage pathway or (b) at least one
dihydrofolate reductase inhibitor or both (a) and (b), thereby
to inhibit nitric oxide synthesis in said cells to ameliorate
said hypotension.
Claim 6. A method of treatment of a subject for systemic
hypotension or expected systemic hypotension caused by
pathological overproduction of nitric oxide from arginine
induced in vascular smooth muscle cells in said subject by
bacterial endotoxins, said method comprising administering to
said subject of a therapeutically effective amount of (a) at
least one guanosine triphosphate pathway tetrahydrobiopterin
synthesis antagonist which is not a reduced pterin that is a
substrate for the pterin salvage pathway or (b) at least one
dihydrofolate reductase inhibitor or both (a) and (b), thereby
to inhibit nitric oxide synthesis in said cells to ameliorate
said hypotension.
Leticia
Appeal No. 1996-3326
Application No. 08/063,067
APJ WALTZ
APJ KRATZ
APJ KIMLIN
DECISION: REVERSED
Send Reference(s): Yes No
or Translation (s)
Panel Change: Yes No
Index Sheet-2901 Rejection(s):
Prepared: September 18, 2001
Draft Final
3 MEM. CONF. Y N
OB/HD GAU
PALM / ACTS 2 / BOOK
DISK (FOIA) / REPORT