Ex Parte Maury et al

Board of Patent Appeals and Interferences

Jul 24, 2007

10721839 (B.P.A.I. Jul. 24, 2007)

The opinion in support of the decision being entered today
is not binding precedent of the Board.

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte WENDY MAURY, JACK STAPLETON, RICHARD ROLLER,
MARK STINSKI, PAUL B. MCCRAY, and BRIAN TACK
__________

Appeal 2007-1621
Application 10/721,839
Technology Center 1600
__________

Decided: July 24, 2007
__________

Before TONI R. SCHEINER, DONALD E. ADAMS, and ERIC GRIMES,
Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to reducing
the infectivity of a virus by administering a chimeric theta defensin peptide.
The Examiner has rejected the claims as obvious. We have jurisdiction
under 35 U.S.C. § 6(b). We affirm.
BACKGROUND
“Antimicrobial peptides have been isolated from plants, insects, fish,
amphibia, birds, and mammals. Although previously considered an
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Application 10/721,839

evolutionarily ancient system of immune protection with little relevance
beyond minimal primary protection, recent developments have found that
mammalian cells express these peptide antibiotics during inflammatory
events such as wound repair, contact dermatitis and psoriasis” (Specification
2, citations omitted).
Thus, antimicrobial peptides “are apparently a primary component of
innate host protection against microbial pathogenesis” (id. at 2). In the prior
art, for example, “[a] series of synthetically derived theta defensins from
rhesus macaques (RTD 1-3) have been shown to exhibit bactericidal
activity” (id. at 9).
The Specification discloses that when theta defensin peptides were
tested for antiviral activity, both the oxidized (linear) and oxidized circular
forms of the peptides “effectively inhibited HIV replication in HeLa cells”
(id. at 10). The Specification discloses methods for inhibiting viral growth
and proliferation by administering any of a number of antiviral peptides
ranging from 13 to 35 amino acids in length, including chimeric
human/rhesus monkey theta defensins having SEQ ID NOS: 31 and 32 (id.
at 3).
DISCUSSION
1. CLAIMS
Claims 1, 9, 18-24, 27, 28, 34-38, and 40 are on appeal. Claims
10-15, 25, 26, and 29-33 are also pending but have been withdrawn from
consideration by the Examiner.
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The claims have not been argued separately and therefore stand or fall
together. 37 C.F.R. § 41.37(c)(1)(vii). We will focus on claim 1, the
broadest claim on appeal, which reads as follows:
1. A method for reducing the infectivity of an enveloped
virus comprising contacting said virus with a first anti-viral
peptide, said peptide comprising a chimeric theta defensin
peptide selected from the group consisting of SEQ ID NO:31
and SEQ ID NO:32

2. PRIOR ART
The Examiner relies on the following reference:
Lehrer WO 02/085401 A1 Oct. 31, 2002
3. OBVIOUSNESS
Claims 1, 9, 18-24, 27, 28, 34-38, and 40 stand rejected under 35
U.S.C. § 103 as obvious in view of Lehrer (Answer 3).
The Examiner cites Lehrer as teaching “the making and use of theta
defensins comprising an amino acid sequence formed from any combination
of two nonapeptides selected from those disclosed as SEQ ID NOs: 19-64 in
the reference. See, e.g., claim 6” (id. at 4). The Examiner states that Lehrer
“teaches that these defensins may be administered to a subject with a viral
infection, [or] facing exposure to viral infection, including infection by
HIV” (id.).
The Examiner concedes that Lehrer “does not verbatim teach the use
of the peptides of SEQ ID NOs: 31 and 32 of the present application” (id.).
Despite this, the Examiner urges that Lehrer suggests administering those
peptides to combat viral infection because Lehrer “teaches the combination
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of any of the specifically disclosed nonapeptides for the formation of a theta
defensin[] for use in the indicated methods” (id.).
The Examiner reasons that although Lehrer “does not lay out each of
the indicated defensin peptides individually, by setting forth the
nonapeptides from which they are made, the reference nonetheless sets forth
a specific set of defensin peptides that may be immediately envisaged by
those of ordinary skill in the art” (id.). The Examiner concludes that Lehrer
therefore teaches that “each of the peptides formed by each combination of
two of the nonapeptides disclosed on pages 7-8 of the reference” would be
useful in treating viral infections, as recited in claim 1 (id.).
To show that a combination of Lehrer’s nonapeptides results in the
peptides of claim 1, the Examiner initially notes that, because Appellants’
claimed peptides are circular, their amino acid sequences can be validly
represented as starting from position 4, as follows (id. at 3):
4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 1 2 3
SEQ ID NO: 31 R–C–L–C–R–R–G–V–C–R–C–I–C–G–R–G–I–C

4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 1 2 3
SEQ ID NO: 32 R–C–I–C–T–R–G–F–C–R–C–I –C–G –R–G–I–C

The Examiner states that when nonapeptides 27 and 34 of Lehrer are
linked, the resulting peptide sequence is identical to that of realigned SEQ
ID NO: 31 (id. at 5), and that the peptide made by linking nonapeptides 18
and 34 of Lehrer demonstrates that SEQ ID NO: 32 “is also among the
defensins contemplated by the Lehrer reference” (id.). The Examiner
concludes that “[t]hose of ordinary skill in the art would have had a
reasonable expectation of success in the disclosed use of such peptides based
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on the suggestion in the reference that each of the defensin peptides derived
from the disclosed nonapeptides would be useful in the claimed methods”
(id.).
We agree with the Examiner that, in view of Lehrer’s teachings, one
of ordinary skill in the art would have considered it obvious to use peptides
with the sequences set forth in SEQ ID NOS: 31 and 32 to reduce the
infectivity of an enveloped virus.
Specifically, Lehrer discloses “using retrocyclin (e.g. RC-101) or a
retrocyclin analog to prevent or treat infection, for example by an enveloped
virus, including enveloped retroviruses, more specifically by HIV-1, HIV-2
and related retroviruses that cause Acquired Immunodeficiency Syndrome
(AIDS)” (Lehrer 6). Lehrer states that “[f]or use in the subject methods, a
naturally occurring or synthetic retrocyclin may be used” (id.).
Lehrer states that “[r]etrocyclins are octadecapeptides that contain two
linked nonapeptides that may be identical or different” (id. at 7). Lehrer
discloses that the nonapeptides making up retrocyclins have a consensus
amino acid sequence (id.), and provides a list of the 46 nonapeptides derived
from the consensus sequence (id. at 7-8). Linking nonapeptide 27 with
nonapeptide 1 yields a sequence identical to SEQ ID NO: 31, when
allowance is made for the circular nature of the peptides.1 Linking

1 The Examiner asserts that the combination of nonapeptides 27 and 34
results in SEQ ID NO: 31 (Answer 5). However, due to an apparent
typographical error, nonapeptide 34 is incorrectly depicted as having the
same sequence as nonapeptide 1, RCICGRGIC (Lehrer 6). Nonapeptide 34
apparently has the sequence RCLCVRGFC, as evidenced by the
modifications to the consensus sequence being listed s “L3, V5, F8” (id.)
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nonapeptide 18 with nonapeptide 1 results in a sequence identical to SEQ ID
NO: 32, when the same circular peptide allowance is made.2
Thus, one of ordinary skill would have recognized that, by following
Lehrer’s explicit directions for making retrocyclins, one would obtain a set
of retrocyclins that included peptides having SEQ ID NOS: 31 and 32.
Because Lehrer teaches “using retrocyclin . . . or a retrocyclin analog to
prevent or treat infection, for example by an enveloped virus” (Lehrer 6), we
agree with the Examiner that one of ordinary skill would have considered it
obvious to contact peptides having SEQ ID NOS: 31 or 32 with an
enveloped virus to reduce the virus’ infectivity.
Appellants argue that, because “findings of fact by the Board of Patent
Appeals and Interferences must be supported by ‘substantial evidence’
within the record . . . , it necessarily follows that an Examiner’s position on
Appeal must be supported by ‘substantial evidence’ within the record in
order to be upheld” by the Board (Br. 3,3 citing In re Gartside, 203 F.3d
1305, 1315, 53 USPQ2d 1769, 1775 (Fed. Cir. 2000)).
We do not agree. Gartside only applies to review of the decisions of
this board by the Court of Appeals for the Federal Circuit. See Gartside,
203 F.3d at 1315, 53 USPQ2d at 1775 (“‘[S]ubstantial evidence’ review
Thus, the actual combination of peptides resulting in SEQ ID NO: 31 is
nonapeptides 27 and 1.
2 Lehrer’s nonapeptide 18 has the sequence RCICTRGFC (Lehrer 8). The
Examiner’s comparison of “Lehrer 18 and 34” to SEQ ID NO: 32
incorrectly shows that Lehrer’s nonapeptide 18 has an L at the third position
(Answer 5; see position “6” in the comparison of Lehrer 18 and 34 to SEQ
ID NO: 32).
3 Appeal Brief filed October 10, 2006.
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applies when the reviewing court must confine its review of agency
factfinding to the record produced by the agency proceeding.”). It does not
apply to review of an Examiner’s rejection by this board. “[T]he conclusion
of obviousness vel non is based on the preponderance of evidence and
argument in the record.” Id. at 1446, 24 USPQ2d at 1445. See also In re
Kahn, 441 F.3d 977, 989, 78 USPQ2d 1329, 1338 (“[T]he Board need only
establish motivation to combine by a preponderance of the evidence to make
its prima facie case.”). In practical effect, this review is less deferential to
the Examiner than the standard urged by Appellants: any decision that is
supported by a preponderance of the evidence is also supported by
substantial evidence.
Appellants argue that, because Lehrer discloses that retrocyclins are a
combination of two nonapeptides selected from a list of 46 nonapeptides
(SEQ ID NOS: 19-64), Lehrer discloses a genus having 46 X 46, or 2116
members (Br. 4). Appellants argue that the Examiner “has found, using
appellants’ claims as a searching point, that SEQ ID NOS:31 and 32 can be
identified as members of the 2000+ peptide genus described by Lehrer, and
appellants do not disagree. However, this is far short of what is needed to
find obviousness in this situation” (id.). Appellants argue that “the question
boils down to whether one of ordinary skill in the relevant art would have
been motivated to select the claimed species from the prior art genus” (id. at
7; see also Reply Br. 5).
Appellants argue that, in determining whether a prior art genus
renders a species claim obvious, the size of the genus “is a relevant factor,
with the larger the genus and the smaller the selection arguing in favor of
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patentability” (Reply Br. 6). Appellants argue that in the instant case “there
is a large genus, and more importantly, no discussion of why the claimed
species would have been selected” (Br. 8), and therefore the Examiner has
not shown sufficient motivation to select the claimed peptides from among
those disclosed in Lehrer (id. at 9).
We do not agree that Lehrer’s disclosure would have failed to provide
sufficient reason to make the peptides of SEQ ID NOs 31 and 32 and use
them to reduce the infectivity of an enveloped virus. Lehrer explicitly states
that retrocyclins are useful for inhibiting enveloped viruses, including HIV
(Lehrer 6), and that such retrocyclins are made by linking any two of 46
explicitly disclosed peptides (id. at 7-8). It is undisputed that selecting the
appropriate peptides from Lehrer’s list of 46 suitable variants results in SEQ
ID NOS: 31 and 32. The reason one of ordinary skill would have selected
the building blocks resulting in the peptides of claim 1 is that Lehrer
disclosed that they were among the peptides suitable for preparing antiviral
peptides.
Moreover, we do not agree that the appealed obviousness rejection
fails to meet the standard set MPEP § 2144.08 and the cases cited therein.
For example, in In re Jones, 958 F.2d 347, 350 21 USPQ2d 1941, 1943
(Fed. Cir. 1992), the court held a species claim to be unobvious over a genus
that was “potentially infinite,” the claimed compound also having significant
structural differences compared to the primary reference. Similarly, in In re
Baird, 16 F.3d 380, 382, 29 USPQ2d 1550, 1552 (Fed. Cir. 1994), the prior
art disclosed a generic formula encompassing “more than 100 million
different diphenols[,]” and the reference’s fifteen preferred compounds did
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not disclose, or even suggest the claimed compound. See also, In re Bell,
991 F.2d 781, 784, 26 USPQ2d 1529, 1531 (Fed. Cir. 1993) (species claim
held unobvious over genus encompassing “more than 1036 different
nucleotide sequences”); In re Deuel 51 F.3d 1552, 1558, 34 USPQ2d 1210,
1215 (Fed. Cir. 1995) (species claim held unobvious over genus
encompassing “an enormous number of DNA sequences”).
Rather than requiring the artisan of ordinary skill to select from a
genus having many millions of possible choices, Lehrer only requires the
practitioner to choose a first nonapeptide from among 46 possibilities, and a
second nonapeptide from the same list of 46 members. Thus, the situation
faced by the artisan of ordinary skill practicing Lehrer’s disclosure is not
analogous to that in Jones, Baird, Bell, and Deuel, in which species claims
were held unobvious over huge genera. Rather, because preparing antiviral
retrocyclins according to Lehrer’s disclosure requires selecting only two
nonapeptides from a list of 46, in our view, the instant situation is more
similar to that of Merck & Co. Inc. v. Biocraft Labs., Inc., 874 F.2d 804,
807, 10 USPQ2d 1843, 1846 (Fed. Cir. 1989).
In Merck, the court held a species claim obvious over a reference
disclosing over 1200 possible combinations of two ingredient types useful in
diuretic compositions, where the claimed combination was one of those
disclosed. Id. at 806-807, 10 USPQ2d at 1845-1846. Neither of the claimed
ingredients was listed by the reference as being preferred. Id. The court
nonetheless held the claims to be obvious in view of the reference’s explicit
teaching that any one of the claimed compositions would produce a diuretic
composition having desirable properties. Id. at 807, 10 USPQ2d at 1845-
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1846. Like the situation in Merck, the artisan of ordinary skill need only
make two choices from a list explicitly set forth in the Lehrer reference. In
our view, the Examiner properly concluded that one of ordinary skill would
have considered claim 1 obvious over Lehrer.
Appellants argue that inhibition of HIV is unpredictable, and that
“[w]here unpredictability undercuts any likelihood of success, as is the case
here, there is no prima facie [case of obviousness]” (Br. 10). Appellants
urge that the unpredictability in the field is demonstrated by Lehrer’s
disclosure that most of the mono-tyrosine substituted retrocyclin variants
were either inactive or only modestly active against HIV-1 strain IIIB, and
that variants RC-106, RC-107, and RC-108 “were not functional against the
JR-CSF strain, either” (Reply Br. 7).
We do not find these arguments persuasive. While Lehrer discloses
that certain tyrosine-substituted peptides were less effective in inhibiting
HIV-1 infection, none of Lehrer’s 46 variations on the retrocyclin consensus
sequence has a tyrosine (Y) substitution (see id. at 7-8). Thus, no member of
Lehrer’s genus has the amino acid substitution urged by Appellants to
undermine the predictability of Lehrer’s disclosure.
Moreover, it is well settled that “[o]bviousness does not require
absolute predictability of success. . . . [A]ll that is required is a reasonable
expectation of success.” In re O’Farrell, 853 F.2d 894, 903-04, 7 USPQ2d
1673, 1681 (Fed. Cir. 1988). In the instant case, claim 1 only requires the
peptide to “reduc[e] the infectivity” of any enveloped virus. Claim 1
therefore encompasses even very small levels of infectivity reduction.
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Lehrer discloses that “[r]etrocyclin was uniformly protective against
both strains of HIV-1 in all of the experiments,” and that certain variants
“showed considerable ability to protect cells from infection by the JR-CSF
strain” (Lehrer 23). Given Lehrer’s explicit disclosure that retrocyclin and
certain variants protected cells from HIV infection, we agree with the
Examiner that one of ordinary skill would have had a reasonable expectation
that selecting from among Lehrer’s list of 46 suitable variants would have
produced a retrocyclin capable of reducing the infectivity of an enveloped
virus, as recited in claim 1.
To summarize, we agree with the Examiner that one of ordinary skill
following Lehrer’s teachings would have considered it obvious to use the
claimed peptides to reduce the infectivity of an enveloped virus. We
therefore affirm the Examiner’s obviousness rejection of claim 1 over
Lehrer. Because they were not argued separately, claims 9, 18-24, 27, 28,
34-38, and 40 fall with claim 1. 37 C.F.R. § 41.37(c)(1)(vii).
AFFIRMED

lbg

STEVEN L. HIGHLANDER, ESQ.
FULBRIGHT & JAWORSKI L.L.P.
SUITE 2400
600 CONGRESS AVENUE
AUSTIN, TX 78701
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