Ex parte BAKER et al.

Board of Patent Appeals and Interferences

Mar 5, 1998

07809039 - (D) (B.P.A.I. Mar. 5, 1998)

Application for patent filed December 16, 1991. 1
According
to applicants, this application is a continuation of
Application 07/670,375, filed March 14, 1991, now abandoned;
which is a continuation of Application 07/060,148, filed June
10, 1987,
now abandoned.
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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(2) is not binding precedent of the Board.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. 34
UNITED STATES PATENT AND TRADEMARK OFFICE
____________
BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
____________
Ex parte PATRICK J. BAKER, MANUEL DEBONO,
KHADIGA Z. FARID and MICHAEL MOLLOY
____________
Appeal No. 94-3007
Application 07/809,0391
____________
ON BRIEF
____________
Before SOFOCLEOUS, Administrative Patent Judge, and
McKELVEY, Senior Administrative Patent Judge, and
GRON, Administrative Patent Judge.
Appeal No. 94-3007
Application 07/809,039
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GRON, Administrative Patent Judge.
DECISION ON APPEAL UNDER 35 U.S.C. § 134
Introduction
This is an appeal from an examiner’s rejections of
Claims 3, 5-7, 12, 14-16, 19, 22, 23, 25-27, 30 and 31, all
claims pending in this application. The claimed compounds and
methods of using the compounds to treat bacterial infections
stand rejected under 35 U.S.C. § 103 as being unpatentable in
view of the structurally similar A-21978C cyclic peptides and
derivative antibacterial agents and intermediates described in
Debono, Re. 32,311, reissued December 16, 1986, and for
obviousness-type double patenting of the A-21978C cyclic
peptide derivatives Debono claims. Independent Claims 30 and
31 are drawn to appellants’ new A-21978C cyclic peptide
derivatives which are described as antibacterial agents or
intermediates to anti-bacterial agents (Specification, page 1,
lines 5-13). Claims 30 and 31 are reproduced in the attached
Appendix.
Discussion
The A-21978C cyclic peptide derivatives described in
Debono differ from the A-21978C cyclic peptide derivatives
encompassed by appellants’ Claim 31 by (1) a single amino acid
Appeal No. 94-3007
Application 07/809,039
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fragment in the otherwise identical cyclic peptide ring, and
(2) an aminoacyl or N-alkanoylaminoacyl cyclic peptide ring
substituent which is characteristic of Debono’s derivatives.
However, the examiner does not cite Debono for its description
of the A-21978C cyclic peptide derivatives Debono describes
and claims which carry a aminoacyl or N-alkanoyl-aminoacyl
ring substituent, but for its description of the A-21978C
cyclic peptides from which Debono’s A-21978C derivatives
were derived. The old A-21978C cyclic peptides appear to
differ from the cyclic peptide compounds
of appellants’ Claim 31 by a single amino acid fragment in
their cyclic peptide rings. The new A-21978C cyclic peptide
derivatives of Claim 31 include the following fragment in
their
cyclic peptide rings:
\
C=O
/
HN
\
CH
/ \
O=C CH2
/ \
HO C=O
/
- NH CH - NH 2
Appeal No. 94-3007
Application 07/809,039
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\ /
C=O .
The old A-21978C cyclic peptides from which the A-21978C
cyclic peptide derivatives Debono claims were derived include
the following fragment as part of their cyclic peptide rings:

\
C=O
/
HN
\
CH
/ \
O=C CH2
/ \
- NH CH - NH C=O2
\ / /
C=O HO .
On the other hand, the new A-21978C cyclic peptide
derivatives defined by appellants’ Claim 30 appear not only to
be anhydrides of the old A-21978C cyclic peptides Debono
describes but, taking into consideration stereoisomerism,
appear also to be anhydrides of the cyclic peptide compounds
defined by appellants’ Claim 31. The compounds of Claim 30
have the following fragment as part of their cyclic peptide
Appeal No. 94-3007
Application 07/809,039
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rings:
\
C=O
/
HN
\
CH
/ \
O=C CH2
/ /
- NH CH - N - C=O2
\ /
C=O .
Other than the examiner’s finding that the compounds of
Claims 30 and 31 are structurally similar to the old A-21978C
cyclic peptides from which Debono derived the A-21978C cyclic
peptide derivatives he describes as antibacterial agents or
intermediates to antibacterial agents, the examiner has
pointed to no teaching in Debono to make and use the new A-
21978C
cyclic peptide derivatives appellants now claim for any reason
whatsoever. Nevertheless, the examiner states (Examiner’s
Answer, the sentence bridging pages 3-4 and the last complete
sentence of page 7), “[A]t col. 17, lines 39-45, Debono
discloses or suggests that certain amino acids used in the
synthesis of the prior art products may exist in its isomeric
Appeal No. 94-3007
Application 07/809,039
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forms,” i.e., the L or D isomers. However, we find that the
compounds of Claim 30 and Claim 31 are more than just optical
isomers of the A-21978C cyclic peptides described in Debono.
They are position isomers.
The examiner next states (Examiner’s Answer, sentence
bridging pages 7-8), “[A]t col. 13, lines 12-25 Debono
suggests cis and trans configuration albeit for the chiral
alkenyl group attached to the N-terminus of an amino acid.”
However, appellants argue that prior art suggestions that the
structural configuration of the side chains of the cyclic
peptide rings of antibacterial agents may be changed without
affecting their antibacterial activity would not have
suggested to persons skilled in the art that changes in the
size and structural configuration of the cyclic peptide rings
of the same compounds can also be made without affecting their
antibacterial activity or utility as intermediates to
compounds displaying antibacterial activity (Appellants’
Brief, page 8; Reply Brief, pages 1-3). Appellants back their
arguments by reference to the history of vancomycin
(Appellants’ Brief, pages 5-8; Reply Brief, page 1-3) as
reported in Harris et al., “Structure of the Glycopeptide
Antibiotic Vancomycin, Evidence for an Asparagine Residue in
Appeal No. 94-3007
Application 07/809,039
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the Peptide,” Journal of the American Chemical Society, Volume
104, page 4293 (1982)(attached to Paper No. 16, filed November
8, 1991) and by the Declaration Under 37 CFR § 1.132 by Manuel
Debono dated September 1, 1992 (Paper No. 21). The examiner
does not contradict appellants’ evidence.
The examiner suggests, however, that the history of
vancomycin is irrelevant to the patentability of the
patentably distinct compounds presently claimed in view of
Debono’s teaching. We disagree. We find that the reported
comparisons of the antibacterial activities of vancomycin to
derivatives thereof, which differ by one amino acid fragment
of their cyclic peptide rings, reasonably would have suggested
to persons having ordinary skill in the art that similar
changes in the structure of the cyclic peptide rings of other
known antibacterial agents would also be likely to affect the
antibacterial activity they exhibit. The evidence to which
the examiner points carries far less weight than the evidence
to which appellants point because it does not focus on the
basic difference between the ring structures of the prior art
compounds and the ring structures of the cyclic peptide
compounds here claimed.
Having considered and weighed all of the evidence
Appeal No. 94-3007
Application 07/809,039
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presented in this case, we find that the examiner’s rejection
of appellants’ claims under 35 U.S.C. § 103 is based
essentially on the examiner’s finding that persons having
ordinary skill in the pertinent art reasonably would have
expected that all new position isomers and/or anhydides of
known compounds would exhibit the same or substantially the
same properties as their known counterpart. In short, the
examiner has in this case applied what appears to this panel
to be a per se rule of obviousness which applies irrespective
of the types of compounds claimed and the weight of the
evidence of record relevant to the patentability issues. To
withhold the patentability of the compounds presently claimed
under 35 U.S.C. § 103 based on a per se rule of obviousness is
a legal error. See In re Ochiai, 71 F.3d 1565, 1572, 37
USPQ2d 1127, 1133 (Fed. Cir. 1995):
The use of per se rules, while undoubtedly less
laborious than a searching comparison of the claimed
invention -- including all its limitations -- with the
teachings of the prior art, flouts section 103 and the
fundamental case law applying it. Per se rules that
eliminate the need for fact-specific analysis of claims
and prior art may be administratively convenient for
PTO examiners and the Board. . . . But reliance on per
se rules of obviousness is legally incorrect and must
cease.
To better understand the examiner’s rejection, we need
Appeal No. 94-3007
Application 07/809,039
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but take a closer look at the examiner’s attempts to explain
the rejection. The examiner states (Examiner’s Answer, page
4):
The compounds of Debono are similar to each of the
claimed compounds in having the known peptide backbone
structure of the cyclized amino acid residues of the
parent A-21978C of formula Trp-Asn-Asp-Thr-Gly-Orn-
Asp-Ala-Asp-Gly-Ser-3MG-OL-Kyn except for the amino
acid residue, Asp, at the ninth position of the claimed
compound 34 which is a beta . . . isomer of aspartyl of
the prior art alpha . . . aspartyl. It would have been
obvious to one of ordinary skill in the art at the time
the invention was made to substitute the amino acid
residue . . . [alpha]-Asp of Debono with its isomer,
. . .[beta]-Asp with a reasonable expectation that said
. . .[beta]-isomer would exhibit a similar antibiotic
property as its . . . [alpha]-counterpart, as suggested
by Debono supra. Further, due to the close structural
similarity and closeness of relationship of the isomers
it is expected that they would possess very close
properties . . . .
We find in the examiner’s statement of the rejection little or
no basis for obviousness other than the structural similarity
between the old and new compounds to explain why the A-21978C
compounds Debono describes would have led persons having
ordinary skill in the art (1) to make appellants’ new
compounds, and (2) to reasonably expect the new compounds also
to be useful as antibacterial agents or as intermediates to
antibacterial agents. We repeat the last sentence of the
examiner’s statement:
Appeal No. 94-3007
Application 07/809,039
Bodanszky et al. (Bodanszky), “Side Reactions in2
Peptide Synthesis,” Synthesis 1981, pages 333-338, 351-356
(May 1981), was first cited by applicants in their Information
Disclosure Statement filed May 4, 1988 (Paper No. 3). First,
we note that the examiner did not mention Bodanszky in the
statement of the rejection. See
In re Hoch, 428 F.2d 1341, 1342 n.3, 166 USPQ 406, 407 n.3
(CCPA 1970)(“Where a reference is relied on to support a
rejection, whether
or not in a ‘minor capacity,’ there would appear to be no
excuse
for not positively including the reference in the statement of
the rejection.”) Second, Bodanszky appears to be providing
peptide chemists with notice of problem side reactions and
undesirable
by-products which they must always consider. Bodanszky
appears to lead skilled artisans away from the side reactions.
Third, while Bodanszky does teach that the Asp residues are
susceptible
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. . . [D]ue to the close structural similarity and
closeness of relationship of the isomers it is expected
that they would possess very close properties . . . .
Next, the examiner states (Examiner’s Answer, pages 4-5,
bridging paragraph):
The compound of claim 30 differs from the compound
of the prior art in that the claimed compound is drawn
to an anhydrous form of the peptide, as opposed to the
prior art hydrated compound. Such difference however
would have been obvious to one of ordinary skill in the
art at the time the invention was made since the claimed
anhydro compound, a transpeptidation reaction
intermediate
between the parent compound and the claimed isomer, is
the
sole pathway to the formation of an aspartyl isomer
product.
(Note the Bodansky [sic, Bodanszky] reference at pp. 336-
338, submitted by appellants.) Also, note the suggested [2]
Appeal No. 94-3007
Application 07/809,039
to cyclization reactions, the author does not indicate whether
Asp residues of cyclic peptides are more or less susceptible
to cyclization side reactions than Asp residues of peptides in
general. On this point, see Debono’s declaration dated
September 1, 1992 (Paper No. 21).
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teachings of Debono, col. 2, lines 3-5, that the A-21978C
cyclic peptides of the prior art are useful as
intermediates.
The evidence in this case appears to support the
examiner’s findings of a close structural similarity and/or a
hydrate/
anhydrate relationship between the prior art compounds and the
compounds appellants claim. We are mindful that close
structural similarity between a prior art compound and a new
compound may, depending on the facts, provide persons having
ordinary skill in the art with all the motivation necessary to
make and use the new compounds with reasonable expectation
that the new compounds would have substantially the same
properties as the old compounds. However, the evidence in
this case as a whole would not have led a person having
ordinary skill in the art to the same conclusion. Here,
secondary evidence of record strongly suggests that minor
changes in the ring structure of a cyclic peptide useful as an
antibacterial agent was known not only to affect the activity
Appeal No. 94-3007
Application 07/809,039
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of the agent but also to render the agent useless for treating
bacteria or for preparing antibacterial agents. Since the
examiner’s case is based entirely on structural similarity,
and he has proffered no evidence to contradict the evidence
favoring patentability, we find that the greater weight of the
evidence of record favors patentability.
In short, persons having ordinary skill in the art,
having prior knowledge of all the evidence of record, would
not have been motivated simply by close structural similarity
to reasonably expect that cyclic peptide ring position isomers
and anhydrides of known prior art antibacterial agents would
be useful in treating bacterial infections. To the contrary,
prior art cyclic peptides which had been similarly modified
had been rendered useless.
We understand the examiner’s apparent view that the close
structural similarity of compounds when considered by artisans
isolated from the knowledge in the art might very well support
a prima facie case of obviousness under 35 U.S.C. § 103. In
this case, however, the examiner must recognize the knowledge
in the art. Persons having ordinary skill in the art bring
all the knowledge in the art with them when reading a
reference. See In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d
Appeal No. 94-3007
Application 07/809,039
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1500, 1502 (Fed. Cir. 1988)(“The board attributes to the
‘hypothetical person’ knowledge of all prior art in the field
of the inventor’s endeavor . . . . That view accords with the
plethora of this court’s precedent.”) The evidence in this
case indicates that persons knowledgeable in the pertinent art
reasonably would not have expected that ring position isomers
and anyhdrides of known A-21978C cyclic peptides would exhibit
antibacterial activity.
Having considered all the evidence, we find that persons
having ordinary skill in the art would not have been motivated
to do what the inventors have done with reasonable expectation
of obtaining a new antibacterial agent. The prior art
teaching as a whole, given the possibility of and the rewards
for success, may have been sufficient to invite skilled
artisans to look at compounds structurally similar to known
antibacterial agents in the hope of finding new antibacterial
agents. However, obvious to try or obvious to experiment is
not the standard for obviousness under 35 U.S.C. § 103. In re
O’Farrell, 853 F.2d 894, 903, 7 USPQ2d 1673, 1681 (Fed. Cir.
1988); In re Dow Chemical Co., 837 F.2d 469, 473, 5 USPQ2d
1529, 1532 (Fed. Cir. 1988). We reverse the examiner’s
rejection of Claims 3, 5-7, 12, 14-16, 19, 22, 23, 25-27, 30
Appeal No. 94-3007
Application 07/809,039
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and 31 under 35 U.S.C. § 103 in view of Debono.
For the reasons stated with regard to the Section 103
rejection, we also reverse the examiner’s rejection of Claims
3, 5-7, 12, 14-16, 19, 22, 23, 25-27, 30 and 31 for
obviousness-type double patenting in view of the compounds
Debono claims. Debono claims A-21978C cyclic peptide
derivatives which, given the proviso in Debono’s Claim 1 which
requires an aminoacyl or
N-alkanoylaminoacyl group in the derivatives, are even less
structurally similar to the cyclic peptides of the claims on
appeal than are the original A-21978C cyclic peptides
themselves.
Conclusion
We reverse the examiner’s rejections of Claims 3, 5-7,
12, 14-16, 19, 22, 23, 25-27, 30 and 31 under 35 U.S.C. § 103
in view of Debono’s teaching and for obviousness-type double
patenting of the compounds Debono claims.
REVERSED
Appeal No. 94-3007
Application 07/809,039
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Michael Sofocleous )
Administrative Patent Judge )
)
)
)
Fred E. McKelvey, Senior ) BOARD OF
PATENT
Administrative Patent Judge ) APPEALS AND
) INTERFERENCES
)
)
Teddy S. Gron )
Administrative Patent Judge )

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