Ex Parte Havenga et al

Board of Patent Appeals and Interferences

Mar 31, 2009

11207626 (B.P.A.I. Mar. 31, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte MENZO HAVENGA, RONALD VOGELS
and ABRAHAM BOUT
__________

Appeal 2008-3811
Application 11/207,626
Technology Center 1600
__________

Decided:1 March 31, 2009
__________

Before TONI R. SCHEINER, DEMETRA J. MILLS, and
RICHARD M. LEBOVITZ, Administrative Patent Judges.

SCHEINER, Administrative Patent Judge.

DECISION ON APPEAL

1 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, begins to run from the decided date
shown on this page of the decision. The time period does not run from the
Mail Date (paper delivery) or Notification Date (electronic delivery).

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This is an appeal under 35 U.S.C. § 134 from the Examiner’s final
rejection of claims 1, 4, 6, 7, and 9-11, all the claims pending. We have
jurisdiction under 35 U.S.C. § 6(b).
STATEMENT OF THE CASE
“Gene-transfer vectors derived from adenoviruses . . . have a number
of features that make them particularly useful for gene transfer . . . [but]
there are still drawbacks associated with the[ir] use” (Spec. ¶ 6). “Typically,
adenoviruses . . . elicit an immune response by a host into which they are
introduced. Also, although the virus generally . . . has a wide infection
range, there is a problem in targeting certain cells and tissues” (id.).
“The [human] adenovirus serotype 5 (“Ad5”) is most widely used for
gene therapy purposes . . . [and] has a natural affiliation towards lung
epithelia and other respiratory tissues” (Spec. ¶ 11). The present invention is
directed to chimeric adenoviruses which “have an altered tropism different
from that of Ad5” (id. at ¶ 45). According to the Specification, a chimeric
adenovirus “based on Ad5 but displaying any [other] adenovirus fiber
existing in nature . . . is able to infect certain cell types more efficiently, or
less efficiently in vitro and in vivo than the [wildtype] Ad5” (id.).
Claims 1 and 4 are representative of the subject matter on appeal, and
read as follows:
1. A recombinant adenovirus of serotype 5 with an altered tropism as
compared to wild-type adenovirus serotype 5, said recombinant adenovirus
comprising:
a chimaeric fiber protein, said fiber protein comprising the knob
domain of a fiber protein from an adenoviral serotype selected from the
group consisting of: adenovirus serotype 12, 16, 32, 40-S, 40-L, 49, and 51.

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4. The recombinant adenovirus of claim 1, wherein said adenovirus
further comprises:
at least a part of a penton or hexon protein, or both, from a third
adenovirus serotype; and
wherein said third adenovirus serotype may be the same as or
different from the serotype of the knob domain.

The Examiner relies on the following evidence:
Crystal et al. (Crystal) US 6,127,525 Oct. 3, 2000
Wickham et al. (Wickham) WO 96/26281 Aug. 29, 1996

Appellants rely on the following additional evidence:

Jason Gall et al. (Gall), Adenovirus Type 5 and 7 Capsid Chimera: Fiber
Replacement Alters Receptor Tropism without Affecting Primary Immune
Neutralization Epitopes, 70(4) JOURNAL OF VIROLOGY 2116-2123 (1996).

Delphine Rea et al. (Rea), Highly Efficient Transduction of Human
Monocyte-Derived Dendritic Cells with Subgroup B Fiber-Modified
Aenovirus Vectors Enhances Transgene-Encoded Antigen Presentation to
Cytotoxic T Cells, 166 JOURNAL OF IMMUNOLOGY 5236-5244 (2001).

The Examiner rejected claims 1, 4, 6, 7, and 9-11 under 35 U.S.C.
§ 103(a) as unpatentable over Crystal and Wickham.
We affirm.
ISSUE ON APPEAL
The issue raised by this appeal is whether Appellants have established
that the Examiner erred in concluding that it would have been obvious for
one of ordinary skill in the art to make a recombinant adenovirus of serotype
5 comprising the knob domain of the fiber protein from adenoviral serotype
12, 16, 32, 40-S, 40-L, 49, or 51.

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FINDINGS OF FACT
FF1 Appellants claim a recombinant adenovirus based on the
serotype 5 adenovirus, but comprising the knob domain of the fiber protein
from an adenovirus serotype selected from the group consisting of serotypes
12, 16, 32, 40-S, 40-L, 49, and 51, where the recombinant adenovirus has an
altered tropism as compared to wild-type adenovirus serotype 5 (claim 1).
The recombinant adenovirus may further comprise “at least a part of a
penton or hexon protein” from an adenovirus serotype “the same as or
different from the serotype of the knob domain” (claim 4). The claims do
not specify any particular change in tropism, i.e., the claims do not specify
whether the change in tropism confers a broader or narrower host range, or
even whether the change is a change in receptor tropism, cellular tropism, or
tissue tropism.
FF2 The capsid of an adenovirus comprises three major structural
proteins, termed pentons, hexons, and fibers. The fiber proteins protrude
from the surface of the capsid, and each fiber consists of a tail, a shaft, and a
knob (Crystal, col. 3, ll. 20-21; Wickham 1: 11-26).
FF3 An adenovirus uses two separate cellular receptors to attach to
and infect a cell (Wickham 2: 13-15). The fiber proteins attach to an
unidentified cellular receptor (id. at 2: 16-18) through a receptor binding
domain localized in the knob region of the fibers, roughly the last 200 amino
acids in the protein (Crystal, col. 3, ll. 27-30; Wickham 2: 37-3: 2). In
addition, the pentons bind to a family of heterodimeric cell-surface
receptors, the αv integrins (Wickham 2: 18-20).
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FF4 At the time of the invention, adenovirus serotypes 2 and 5
(Ad2 and Ad5) were “well characterized,” and were the two serotypes
“employed for gene transfer studies, including human gene therapy trials”
(Crystal, col. 1, ll. 51-54).
FF5 It was known that the development of neutralizing antibodies to
antigenic epitopes on adenoviral capsid proteins could limit the ability of a
given adenoviral vector to be used more than once as an effective gene
transfer vehicle (Crystal, col. 2, ll. 19-24).
FF6 It was also known that “[t]he hexon protein, and to a lesser
extent the fiber protein, comprise the main antigenic determinants” of
adenoviruses (Crystal, col. 2, ll. 46-48). “Furthermore, all adenovirus
serotypes appear to possess a type of specific moiety located in the knob
region” (id. at col. 3, ll. 32-34).
FF7 According to Crystal, “switching the fiber from that of
adenoviral serotype 5 group C vector to that of an adenoviral serotype 7
group B vector by itself is insufficient to allow the vector to escape
neutralizing antibodies generated against an adenoviral vector comprising
Ad5 fiber” (Crystal, col. 25, ll. 15-19). However, Crystal teaches that a
recombinant adenovirus with “a decreased ability or inability to be
recognized by neutralizing antibodies directed against the corresponding
wild-type coat protein” can be made by replacing the both the native fiber
and hexon proteins of the wild-type adenovirus, in their entirety, with fiber
and hexon proteins from a different serotype (id. at col. 16, ll. 5-17; col. 27,
l. 66 to col. 28, l. 8).
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FF8 Further according to Crystal, the native adenovirus of the
recombinant adenoviral vector is preferably Ad2 or Ad5 (Crystal, col. 15, l.
10), while the adenovirus coat proteins preferably come from “Ad1, Ad2,
Ad3, Ad5, Ads, Ad7, Ad11, Ad12, Ad14, Ad16, Ad21, Ad34, Ad35, Ad40,
Ad41, or Ad48” (Crystal, col. 4, ll. 38-41).
FF9 Thus, Crystal suggests making a recombinant adenoviral vector
with a decreased ability to be recognized by neutralizing antibodies, for use
in gene therapy, by replacing the fiber and hexon proteins of adenovirus
serotype Ad2 or Ad5 (the two serotypes used in gene therapy) with the fiber
and hexon proteins (the main antigenic determinants) from sixteen
adenovirus serotypes, of which three - Ad12, Ad16, and Ad40 - are the same
as those encompassed by the present claims (FF1, 4, 6, 7, 8).
FF10 Another recognized “drawback of using recombinant
adenovirus in gene therapy is that all cells that express the aforementioned
two receptors used by adenovirus to attach and infect a cell will internalize
the gene(s) being administered - not just the cells in need of therapeutic
treatment” (Wickham 5: 24-29). On the other hand, “certain cells, such as
lymphocytes, which lack the αv integrin adenoviral receptors . . . are not
readily amenable to adenovirus-mediated gene delivery” (id. at 5: 29-34).
FF11 Wickham describes a method of making a chimeric adenoviral
vector “capable of avoiding neutralizing antibodies upon repeat
administration” and/or capable of “target[ing] gene therapy to selected
cells/tissues” (Wickham 6: 33 to 7: 3). The chimeric adenoviral vector has a
fiber protein “which differs from the native (wild-type) fiber protein by the
introduction of a nonnative amino acid sequence” (id. at 7: 22-24).
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FF12 According to Wickham, a “‘[n]onnative amino acid sequence’
includes an amino acid sequence from an adenoviral serotype other than the
serotype of the adenovirus with the chimeric fiber protein . . . . For example,
an Ad3 fiber amino acid sequence or the entire Ad3 fiber expressed in an
Ad5 chimeric fiber protein or in place of an Ad5 fiber protein” (Wickham 9:
32-37).
FF13 Wickham describes a recombinant adenovirus in which the
native Ad5 receptor domain of the fiber protein is replaced with the Ad3
receptor binding domain (Wickham, Example 2). According to Wickham,
The receptor for Ad3 contains a sialic acid component, which is
required for binding of Ad3, while binding of Ad5 does not
involve sialic acid. Since sialic acid is found on all higher
eukaryotic cells, the Ad3/Ad5 fiber chimera is capable of
binding to all cells. Such a vector can infect a broader range of
cell types and exhibits different tissue specificity than non-
chimeric Ad5 vectors in vivo.

(Id. at 24: 7-10.)
FF14 Wickham also describes an adenoviral vector in which the
native Ad5 fiber is replaced with the Ad7 fiber, i.e., a Ad5/7 chimera
(Wickham, Example 7). According to Wickham,
The replacement of the wild-type Ad5 fiber gene with that of
Ad7 did not impair the ability of the virus to infect cells
. . . the virus in which the native fiber was replaced with a
nonnative fiber could also infect cells and express genes like the
parental virus in vivo.

(Id. at 29: 26-31.)
FF15 Gall confirms Wickham’s observations with respect to the
Ad5/7 chimera. Although “[c]ompetition assays indicate that Ad5 and Ad7
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enter A549 cells through different primary receptors” (Gall 2121, col. 1),
and replacing the Ad5 fiber protein with the Ad7 fiber protein results in
chimeric vector with an altered receptor tropism (id. at 2118, col. 2),
[S]tudies on gross infection of the heart, liver, and lung suggest
that the majority of cells available for infection in all likelihood
contain receptors for both Ad5 and Ad7 receptors present in
functionally equal numbers. Assuming that future in vivo
studies support the data presented in this study with respect to a
strong cellular colocalization of Ad5 and Ad7 receptors,
differences in tissue tropism for wild-type Ad 5 and Ad7 must
be due to events subsequent to virus attachment and entry.

(Id. at 2121, col. 1.)
FF16 Rea teaches that the fiber protein is “an important determinant
for Ad attachment and natural tropism, . . . [and] an attractive target for
modifying cell specificity and transduction properties of rAd5” (Rea 5242,
col. 2).
To date, 51 serotypes of human Ad have been identified and
divided into six subgroups from A to F. Their entry into
susceptible cells is a two-step process consisting of virus
attachment to the membrane via the Ad fiber knob, followed by
internalization upon binding of the penton base RGD motifs to
cellular integrins. Although the penton-integrin interactions
may represent a common pathway for internalization,
attachment strategies vary among Ad subgroups and play an
important role in dictating Ad tropism. In this regard, the fiber
is a crucial mediator for high-efficiency binding to target cells.

(Rea 5236, col. 2 (internal citations omitted).)
FF17 Rea “demonstrate[s] that replacement of the Ad5 fiber by fibers
from subgroup B Ad16, 35, and 50, but not by fibers from other Ad
subgroups, dramatically increases the efficiency of rAd5-mediated gene
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transfer into human DC” (Rea 5242, col. 2). “In addition to targeting DC
more efficiently,
rAd5 with subgroup B fibers conserve the immune-activating
properties of the rAd5 parental virus. These novel vectors
increase the expression of co-stimulatory and MHC molecules
on DC an act in synergy with LPS to promote the maturation of
DC into fully immunostimulatory APC [antigen presenting
cells]. In fact, due to more efficient infection, subgroup B
fiber-modified rAd5 exert an enhanced effect on DC
maturation. Altogether, these characteristics lead to a better
presentation of the transgene-encoded Ag to specific T cells, a
key issue for rAd-infected DC-based immunization strategies.

[These] findings demonstrate major progress toward the clinical
applicability of rAd vectors as vaccines to battle cancer and
pathogens and support the use of subgroup B fiber-modified
viruses, especially rAd5F35, for ex vivo Ag delivery into DC.
Moreover, the favorable kinetics of DC infection by rAd5F35
even in the presence of other susceptible cells may enable this
vector to reach the DC network in vivo and suggest that this
vector is an attractive new genetic vaccine.

(Id. at 5243, col. 1.)
PRINCIPLES OF LAW
The question of obviousness is resolved on the basis of underlying
factual determinations including: (1) the scope and content of the prior art;
(2) the level of ordinary skill in the art; (3) the differences between the
claimed invention and the prior art; and (4) evidence of secondary factors,
also known as objective indicia of nonobviousness, if any. Graham v. John
Deere Co., 383 U.S. 1, 17-18 (1966).
“[A]ny need or problem known in the field of endeavor at the time of
invention and addressed by the patent can provide a reason for combining
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the elements in the manner claimed.” KSR Int’l v. Teleflex Inc., 550 U.S.
398, ___, 127 S. Ct. 1727, 1742 (2007). As long as some suggestion to
combine the elements is provided by the prior art as a whole, the law does
not require that they be combined for the reason or advantage contemplated
by the inventor. In re Beattie, 974 F.2d 1309, 1312 (Fed. Cir. 1992); In re
Kronig, 539 F.2d 1300, 1304 (CCPA 1976).
Once the Examiner makes out a prima facie case of unpatentability,
“the burden of coming forward with evidence or argument shifts to the
applicant. After evidence or argument is submitted by the applicant in
response, patentability is determined on the totality of the record, by a
preponderance of evidence with due consideration to persuasiveness of
argument.” In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992).
Finally, a showing of unexpected results must be “commensurate in
scope with the degree of protection sought by the claimed subject matter” to
be persuasive of non-obviousness. In re Harris, 409 F.3d 1339, 1344 (Fed.
Cir. 2005).
ANALYSIS
The Examiner concluded that it would have been obvious for one of
ordinary skill in the art to “generat[e] a chimeric adenovirus comprising the
fiber of Ad 12, 16, or 40 . . . because Crystal et al teach that it is within the
ordinary skill of the art to use the fibers of Ad 12, 16, or 40 to generate
adenoviruses with chimeric coat proteins for altered antigenicity” and a
change in tropism would not have been unexpected “because Wickham et al
teach that it is within the ordinary skill of the art to use chimeric fibers for
altered tropism and antigenicity” (Ans. 5).
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Appellants contend that Crystal is focused on modifying adenoviral
proteins in order to avoid neutralizing antibodies, and does not teach that
swapping fiber proteins would result in an altered tropism (App. Br. 5).
Moreover, Appellants contend that Crystal teaches away from swapping
fiber proteins at all, since Crystal discloses that swapping fiber proteins “by
itself is insufficient to allow the vector to escape neutralizing antibodies” (id.
at 15).
Appellants contend that Crystal and Wickham “cannot be combined to
make obvious an altered tropism of a chimeric adenovirus through the
incorporation of portions of a fiber protein . . . as no reasonable expectation
of success exists in so doing” (App. Br. 8). Appellants contend that
“Wickham provide[s] no firm indication . . . that the tropism of an
adenovirus can be changed through the use of a chimeric fiber protein” (id.
at 9), because “Wickham describes three adenoviruses with chimeric tail
proteins (Ad5/2, Ad5/3, and Ad5/7) . . . [and] obtains a different result in
regard to a change in tropism” for each (id. at 8). Specifically, Appellants
contend that “substitution of an Ad2 fiber protein for the native Ad5 fiber
protein results in no change of tropism” (id.), “substitution of an Ad7 fiber
protein for the native Ad5 fiber protein results in a change in the receptor
that was targeted by the virus, but . . . [there is] no indication whether the
resulting chimeric virus has changed its tropism” (id. at 9), and Wickham
only “hypothesizes that the creation of an Ad5/Ad3 chimeric fiber protein
would result in a change of tropism for the resulting chimeric virus” (id.).
Appellants contend “[t]his lack of change in tropism is confirmed by Gall”
(App. Br. 9), since “Gall shows that the parent [Ad5] vector as well as the
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Ad5/7 chimera can infect cells from . . . [heart, liver, and lung] tissues. But,
notably, it was again not demonstrated that the chimeric vector could infect
other cells better than the parent Ad5 vector” (id.).
These arguments are not persuasive. It is true that Crystal does not
discuss altered tropism, but it is well settled that the prior art need not
suggest combining teachings in the art for the same reason or advantage
asserted by Appellants (see Beattie, 974 F.2d at 1312; Kronig, 539 F.2d at
1304). It is also true that Crystal teaches that replacing the fiber protein of
Ad5 with the fiber protein of Ad7, by itself, does not allow the recombinant
vector to evade anti-Ad5 neutralizing antibodies (FF7). However, Crystal
teaches that the main adenoviral antigenic determinants are the hexon and
fiber proteins, and discloses recombinant adenoviral vectors where both the
fiber (including the knob domain) and hexon proteins are chimeric (FF7).
As discussed above, the present claims encompass adenoviral vectors where
both the hexon and fiber proteins are chimeric (FF1). Moreover, the fact
that Gall confirms Wickham’s observations with respect to the Ad5/7
chimera (i.e., that replacing the fiber protein of Ad5 with the fiber protein
from Ad7 alters receptor tropism, but not gross infectivity of heart, liver, and
lung tissue) (FF15) is simply not relevant to how one of skill in the art
would view Wickham’s assertion that an Ad5/3 chimera will infect a broader
range of cell types and exhibit different tissue specificity than a non-
chimeric Ad5 vector (FF13).
Appellants further contend that Wickham “is worried about non-
specific binding of adenoviruses” (Reply Br. 10), thus, an Ad5/3 chimeric
adenovirus “would have the opposite effect of what is desired: if Wickham
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is correct in the statement that all cells contain the sialic component (and the
skilled person has no reason to think otherwise), ALL cells in a eukaryotic
host can be infected by an Ad5-Fiber 3 chimeric virus and the occurrence of
unwanted side effects is anything but circumvented” (id. at 11).
This argument is beside the point - the present claims require only “an
altered tropism,” not a narrowed tropism. If Wickham is correct, then the
Ad5/3 chimeric vector will have a broader host range than the parent vector,
and a broader tropism is still “an altered tropism.”
In addition, Appellants contend that Crystal “does not provide a
teaching or suggestion to arrive at any specific combination of serotypes”
(id. at 7), and “at most, suggests the use of 3 different coat proteins, from 16
different serotypes, . . . for use in any of 49 other serotypes; giving a
combination of 2352 ‘suggested’ chimeric viruses, of which applicants claim
three” (id.). Appellants contend that it would not have been obvious to “try
each of the numerous possible choices, until a combination that actually
altered tropism was arrived at” (id. at 11-12), because “swapping fiber
proteins or creating chimeric fiber proteins were neither an identified nor
predictable solution to altering viral tropism at the time the application was
filed” (id. at 11).
This argument is not persuasive. Again, the prior art need not suggest
combining teachings in the art for the same reason or advantage asserted by
Appellants. In any case, Crystal suggests a more limited number of
combinations than that alleged by Appellants in order to make recombinant
adenoviruses capable of evading neutralizing antibodies. The relevant
number of base serotypes is, at most, two, Ad2 and Ad5, because these are
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the two serotypes Crystal identifies as being used in gene therapy (FF4,
FF8). Moreover, Crystal teaches that the hexon and fiber proteins are the
most antigenic of the coat proteins (FF6). That leaves sixteen serotypes as
the source of the chimeric coat proteins, three of which are the same as the
serotypes required by the claims (FF8).
We agree with the Examiner that Crystal suggests making a
recombinant adenovirus using Ad5 as the base virus, and inserting the fiber
and hexon proteins from a small group of serotypes including serotypes 12,
16, and 40, in order to obtain an adenoviral vector capable of evading
neutralizing antibodies directed against wild-type Ad5. The question that
remains is whether Appellants have demonstrated that any altered tropism of
the resultant recombinant adenoviruses would have been unexpected, given
the state of the art at the time of the invention, and keeping in mind that the
claims do not specify any particular change in tropism, i.e., whether the
change in tropism confers a broader or narrower host range, or even whether
the change is a change in receptor tropism, cellular tropism, or tissue tropism
(FF1).
Appellants contend that “Gall teaches that ‘[t]he predominant
functional change in virus infectivity which results from fiber gene
replacement is altered binding affinity for the target receptor on the surface
of the cell membrane.’ Thus, Gall teaches that one of ordinary skill in the
art . . . would expect a change in receptor affinity not a change in tropism to
a different cell or tissue type” (App. Br. 12). Thus, “any actual change in
tropism to a different cell type is an unexpected result” (id. at 12-13).
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Again, this argument is not persuasive. The fact the Gall confirms
Wickham’s observations regarding the Ad7/5 chimera has no bearing on
Wickham’s assertions regarding the Ad5/3 chimera. Furthermore, claim 1
does not restrict the tropism to different tissue or cell type, but would
include tropisms that involved a change in receptor specificity.
In addition, Appellants contend that an altered tropism would have
been expected because Wickham teaches that the fibers of all adenovirus
serotypes are interchangeable “[w]ith respect to displaying an altered
tropism” (App. Br. 5). In support of this contention, Appellants cite the
following annotated excerpt of Wickham: “[b]ased upon the high degree of
structural similarity between the fiber molecules of the more than 41 human
serotypes of adenovirus, it is expected that any one of the serotypes of human
or nonhuman adenovirus may be used as the source of the fiber gene [i.e.,
they are all interchangeable]” (App. Br. 5 (quoting Wickham at 13: 16-20,
material in brackets inserted by Appellants)).
This argument is not persuasive. This particular excerpt of Wickham
does not concern tropism at all, or even antigenicity, rather it concerns the
facility with which one fiber protein can be swapped with another due to the
gross structural similarities between fiber proteins from different serotypes
and/or subgroups.
Finally, Appellants contend that “[t]he nonobviousness of the present
invention is demonstrated in . . . the Rea et al. publication, which states: ‘Thus,
subgroup B fiber-modified rAd5 constitute a major breakthrough in the
exploitation of ex vivo rAd-targeted DC [Dendritic Cells] as clinically relevant
vaccines and may also be suitable for in vivo genetic modification of DC’”
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(App. Br. 13 (quoting Rea at 5236 (emphasis and bracketed material added by
Appellants))).
Nevertheless, we do not agree that Rea provides persuasive evidence that
it would have been unexpected that swapping fiber proteins would result in
some degree of change in tropism. Again, the present claims broadly require
“an altered tropism” (FF1), and Rea specifically teaches that fiber proteins play
an important roll in dictating adenoviral tropism (FF16). Second, while Rea
reports striking success in targeting clinically important dendritic cells more
efficiently (which can be infected with Ad5, from subgroup C, although
inefficiently), and in promoting their maturation into fully immunostimulatory
APCs (FF17), by substituting fiber proteins from subgroup B (including Ad16)
for the Ad5 fiber protein (FF17), these results are not commensurate in scope
with the claims. Appellants have not explained how Rea’s results are
commensurate in scope with the full scope of the claims, a necessary condition
to rebut prima facie obviousness of the claimed subject matter. See Harris,
409 F.3d at 1344 (Fed. Cir. 2005). As discussed above, the present claims are
quite broad in not specifying the nature of the altered tropism, or even whether
the chimeric adenoviruses have a broader or narrower host range than the
parent adenovirus.
CONCLUSIONS OF LAW
Appellants have not established that the Examiner erred in concluding
that it would have been obvious for one of ordinary skill in the art to make a
recombinant adenovirus of serotype 5 comprising the knob domain of the
fiber protein from adenoviral serotype 12, 16, or 40.

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SUMMARY
We affirm the rejection of claims 1, 4, 6, 7, and 9-11 under 35 U.S.C.
§ 103(a) as unpatentable over Crystal and Wickham.

TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with this
appeal may be extended under 37 C.F.R. § 1.136(a)(1)(iv)(2006).

AFFIRMED
LP

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