Ex Parte Berg et al

Board of Patent Appeals and Interferences

Jul 9, 2010

10363517 (B.P.A.I. Jul. 9, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte EINAR SVERRE BERG and KJELL SKAUG
__________

Appeal 2010-001203
Application 10/363,517
Technology Center 1600
__________

Before DEMETRA J. MILLS, FRANCISCO C. PRATS, and
MELANIE L. McCOLLUM, Administrative Patent Judges.

MILLS, Administrative Patent Judge.

DECISION ON APPEAL1

This is an appeal under 35 U.S.C. § 134. The Examiner has rejected
the claims for obviousness. We have jurisdiction under 35 U.S.C. § 6(b).

1 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, or for filing a request for rehearing,
as recited in 37 C.F.R. § 41.52, begins to run from the “MAIL DATE”
(paper delivery mode) or the “NOTIFICATION DATE” (electronic delivery
mode) shown on the PTOL-90A cover letter attached to this decision.
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STATEMENT OF CASE
The following claim is representative.
20. A method of providing and using an internal control in a nucleic acid-
based analysis of a sample, the method comprising
adding non-viable liposome particles, each non-viable liposome
particle comprising an internal control (IC) nucleic acid, to a sample in
which a target nucleic acid is contained within a target entity
wherein the internal control nucleic acid can be distinguished from the
target nucleic acid, and
wherein said non-viable liposome particles are designed or modified
such that said non-viable liposome particles have a density, weight, or size
which is sufficiently similar to the target entity to allow co-separation in a
density, weight, or size based separation method, and such that said non-
viable liposome particles and said target entities are able to undergo all of
the same treatment steps;
co-separating the target entity and the non-viable liposome particles
from the sample; and using the IC nucleic acid as an internal control in an
analysis of the target nucleic acid.

Additional Appealed claims may be found in the Claims Appendix to the
Brief.
Cited References
Levine et al. US 5,593,848 Jan. 14, 1997
Pasloske et al. US 5,939,262 Aug. 17, 1999

Lopez-Saura et al., Analytical Fractionation of Cultured Hepatoma Cells
(HTC Cells), 543 BIOCHIMICA ET BIOPHYSICA ACTA 430-449 (1978).

Mader et al., Stabilizing effect of an S-layer on liposomes towards thermal
or mechanical stress, 1418 BIOCHIMICA ET BIOPHYSICA ACTA 106-116
(1999).

Meyer et al., Cationic Liposomes Coated with Polyethylene Glycol As
Carriers for Oligonucleotides, 273 J. BIOLOGICAL CHEMISTRY 15621-15627
(1998).
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Pasloske et al. (II), Armored RNA Technology for Production of
Ribonuclease-Resistant Viral RNA Controls and Standards, 36 J. CLINICAL
MICROBIOLOGY 3590-3594 (1998).

Grounds of Rejection
1. Claims 20, 23, 24, 28-30, 38-41, 43-46, and 57-61 are rejected under 35
U.S.C. § 103(a) as being unpatentable over Pasloske in view of Levine.
2. Claim 25 is rejected under 35 U.S.C. § 103(a) as being unpatentable over
Pasloske in view of Levine and further in view of Lopez-Saura.
3. Claims 31-34 are rejected under 35 U.S.C. § 103(a) as being unpatentable
over Pasloske in view of Levine and Mader.
4. Claims 21 and 31-37 are rejected under 35 U.S.C. § 103(a) as being
unpatentable over Pasloske in view of Levine and further in view of Meyer.
5. Claim 42 is rejected under 35 U.S.C. § 103(a) as being unpatentable over
Pasloske in view of Levine and further in view of Pasloske II.

Discussion
1. Claims 20, 23, 24, 28-30, 38-41, 43-46, and 57-61 are rejected under 35
U.S.C. § 103(a) as being unpatentable over Pasloske in view of Levine.

ISSUE
The Examiner concludes that it would have been prima facie obvious
for one of ordinary skill in the art at the time of invention to apply the
teachings of Levine to the method taught by Pasloske.
The Examiner finds that
Since Levine taught that the specific gravity of liposomes was
determined primarily by the density of the encapsulated
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substance (column 1, lines 52-58), an ordinary artisan would
have recognized that without modification, the liposome-
encapsulated nucleic acids of Pasloske would not pellet (i.e. co-
separate) with target entities such as cells or viral particles
encapsulating the target nucleic acids of interest. In other words,
since the methods of Pasloske required co-separation of the
reference and target entities encapsulating the control and target
nucleic acids via centrifugation (column 26, lines 32-38), the
teachings of Levine would have motivated an ordinary artisan to
ensure that the densities of the target entity and liposome-
encapsulated nucleic acids were as closely matched as possible,
specifically by increasing the density of the liposome particles
using a dense filler solution.

(Ans. 7-8.)
Appellants contend that
Pasloske does not disclose or suggest non-viable liposome
particles, wherein said non-viable liposome particles are
designed or modified such that said non-viable liposome particles
have a density, weight, or size which is sufficiently similar to the
target entity to allow co-separation in a density, weight, or size
based separation method, and such that said non-viable liposome
particles and said target entities are able to undergo all of the
same treatment steps.

(App. Br. 9.)
The issue is: Does Pasloske in view of Levine suggest non-viable
liposome particles, wherein said non-viable liposome particles are designed
or modified such that said non-viable liposome particles have a density,
weight, or size which is sufficiently similar to the target entity to allow co-
separation in a density, weight, or size based separation method, and such
that said non-viable liposome particles and said target entities are able to
undergo all of the same treatment steps.
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FINDINGS OF FACT
1. The Examiner finds that Pasloske teaches a method of providing and
using an internal control in a nucleic acid-based analysis of a sample,
comprising:
(a) obtaining a sample to be analyzed (column 26, lines
15-25)
(b) adding an encapsulated internal control (IC) nucleic
acid to a sample in which a target nucleic acid is contained in a
target entity (see column 26, lines 15-39, where an encapsulated
RNA standard is added to a sample containing target nucleic
acids contained within HIV virions; column 11, lines 32-42 teach
that the RNA standard may be encapsulated in a liposome),
wherein the internal control can be distinguished from the
target nucleic acid (see column 26, lines 20-33 and also column
21, line 60 - column 22, line 4),
wherein the encapsulated internal control is sufficiently
similar to the target entity to permit co-separation from the
sample together with the target entity (column 26, lines 32-38)
(c) co-separating the target entity and the liposome
particles from the sample using a centrifugation step (column 26,
lines 32-38)
(d) inducing the release of the target and internal control
nucleic acids (see column 25, lines 31-46)
(e) analyzing the target nucleic acid and the internal
control nucleic acid, thereby using the internal control nucleic
acid as an internal control for analysis of the target nucleic acid
(see column 26, lines 32-50, column 25, lines 20-30, and column
25, line 45 - column 26, line 2).

(Ans. 5.)
2. The Examiner finds, “see Example XXVII (columns 43-44), where
Pasloske teaches adding a RNase-resistant (e.g. liposome-encapsulated - see
column 11, lines 32-42) internal control nucleic acid to a plasma or cell
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sample containing target RNA, copurifying the internal standard and target
RNA, and conducting RT-PCR.” (Id. at 5-6.)
3. The Examiner finds that
Pasloske teaches that the entity encapsulating the internal
standard is disrupted under the same conditions as the target
entity and is selected to have a stability under assay conditions
that is similar enough to the target entity to permit the IC nucleic
acid to undergo the same treatment steps (column 25, lines 20-
46, column 15, lines 6-29, and column 43, line 55 - column 44,
line 5[,] teach disruption of the target entity and entity
encapsulating the internal control nucleic acid under the same
conditions). Therefore, the target and internal control-
encapsulating entity have stabilities that are similar enough to
permit processing under the same conditions.

(Ans. 6.)
4. The Examiner finds that
Pasloske teaches encapsulation of the internal control
RNA molecule in liposomes (column 11, lines 31-39 and
column 14, line 29 - column 15, line 55), but does not teach
designing or modifying the liposomes such that they have a
density, weight, or size that is sufficiently similar to the target
entity to permit co-separation of the encapsulated internal
control and target nucleic acids.

(Id.)
5. “Pasloske also does not teach that the liposomes are designed or
modified to contain molecules specific to the target entity to permit co-
separation by affinity separation.” (Id.)
6. The Examiner finds that
Levine teaches that the specific gravity of liposomes is
determined by the density of the material encapsulated therein
and may be modified by using fillers of different, pre-
determined specific gravities (see column 1, line 54 - column 2,
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line 2). Levine also teaches a specific example wherein
liposomes are filled with a material having a specific,
predetermined density in order to achieve the desired separation
properties by centrifugation (column 4, lines 9-44).

(Id.)
7. The Examiner finds that
Levine additionally teaches that the surfaces of liposomes may
be modified to contain antibodies specific to molecules found on
particular target cells (column 1, lines 32-47 and column 2, lines
2-18). Levine teaches that these antibodies may be used to co-
separate a liposome and target cell via affinity separation
(column 1, lines 32-47 and column 2, lines 2-18).

(Ans. 7.)
8. The Examiner concludes that
It would have been prima facie obvious for one of
ordinary skill in the art at the time of invention to apply the
teachings of Levine to the method taught by Pasloske. Since
Levine taught that the specific gravity of liposomes was
determined primarily by the density of the encapsulated
substance (column 1, lines 52-58), an ordinary artisan would
have recognized that without modification, the liposome-
encapsulated nucleic acids of Pasloske would not pellet (i.e. co-
separate) with target entities such as cells or viral particles
encapsulating the target nucleic acids of interest. In other words,
since the methods of Pasloske required co-separation of the
reference and target entities encapsulating the control and target
nucleic acids via centrifugation (column 26, lines 32-38), the
teachings of Levine would have motivated an ordinary artisan to
ensure that the densities of the target entity and liposome-
encapsulated nucleic acids were as closely matched as possible,
specifically by increasing the density of the liposome particles
using a dense filler solution.

(Id. at 7-8.)
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9. The Examiner further concludes that “An ordinary artisan would have
had a reasonable expectation of success in applying the teachings of Levine
to the method of Pasloske, because Levine successfully controlled the
centrifugation behavior of liposomes by including a dense filler material (see
column 4, lines 9-44).” (Id. at 8.)

10. The Examiner concludes that
An ordinary artisan also would have been motivated by
the teachings of Levine to modify the liposomes of Pasloske by
attaching an antibody to a surface antigen found on the target
entity to permit co-separation of the target entity and liposome
via affinity separation. An ordinary artisan would have
recognized that antibody-based separation methods were more
specific than separation methods based solely on centrifugation,
and therefore, would have been motivated to co-separate the
target entity and the liposome via an affinity-based separation
method using antibodies attached to the liposome surface with a
reasonable expectation of success.

(Ans. 8.)

PRINCIPLES OF LAW
“In rejecting claims under 35 U.S.C. § 103, the examiner bears the
initial burden of presenting a prima facie case of obviousness. Only if that
burden is met, does the burden of coming forward with evidence or
argument shift to the applicant.” In re Rijckaert, 9 F.3d 1531, 1532, (Fed.
Cir. 1993) (citations omitted). In order to determine whether a prima facie
case of obviousness has been established, we consider the factors set forth in
Graham v. John Deere Co., 383 U.S. 1, 17 (1966): (1) the scope and content
of the prior art; (2) the differences between the prior art and the claims at
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issue; (3) the level of ordinary skill in the relevant art; and (4) objective
evidence of nonobviousness, if present.
Moreover, “obviousness requires a suggestion of all limitations in a
claim.” CFMT, Inc. v. Yieldup Int’l. Corp., 349 F.3d 1333, 1342 (Fed. Cir.
2003) (citing In re Royka, 490 F.2d 981, 985 (CCPA 1974)).
When evaluating claims for obviousness, “the prior art as a whole
must be considered. The teachings are to be viewed as they would have
been viewed by one of ordinary skill.” In re Hedges, 783 F.2d 1038, 1041
(Fed. Cir. 1986).
“[T]here must be some articulated reasoning with some rational
underpinning to support the legal conclusion of obviousness.” In re Kahn,
441 F.3d 977, 988 (Fed. Cir. 2006).

ANALYSIS
Obviousness
Appellants contend that
Pasloske does not disclose or suggest non-viable liposome
particles, wherein said non-viable liposome particles are
designed or modified such that said non-viable liposome particles
have a density, weight, or size which is sufficiently similar to the
target entity to allow co-separation in a density, weight, or size
based separation method, and such that said non-viable liposome
particles and said target entities are able to undergo all of the
same treatment steps.

(App. Br. 9.)
Appellants submit that a skilled person would not have
necessarily recognized the need to modify the internal control
particle from reading of Pasloske et al. The tailoring of the
internal control particles as in the claimed invention allows for an
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internal control that can monitor the efficiency of the various
early stages of the analysis of a target nucleic acid contained
within a target entity, i.e., during the storage, transportation,
cell/virus enrichment, and lysis. Particularly, the cell/virus
enrichment stage of analysis may require a step of centrifugation
or of immunocapture and the engineering of the internal control
particle may be necessary in order to monitor the efficiency of
this stage.

(Reply Br. 4.)
Appellants further argue that
Although Pasloske et al, in Example II, Section 2. (col. 26,
lines 15-38), describe the centrifugation of the Armored RNA
internal control and HIV to concentrate the HIV sample, the
Armored RNA internal control particle has not been modified to
exactly match the HIV particles. In this regard, the internal
control MS2 virus particles are tiny (diameter about 30 nm) and
the target HIV particles are at least 4 times larger (diameter about
120 nm). Thus, although the two different particles may both
sediment, the Armored RNAI/synthetic MS2 virus will sediment
more slowly than HIV under the same conditions and an exact
surveillance of the sedimentation efficiency is not possible.
Pasloske et al however does not teach that any modification
should be made to the Armored RNA to improve the method.

(Id. at 4-5.)
We find that the Examiner has provided sufficient evidence that it was
known in the prior art to select non-viable liposome particles having a
density, weight, or size which is sufficiently similar to the target entity to
allow co-separation in a density, weight, or size based separation method,
and such that said non-viable liposome particles and said target entities are
able to undergo all of the same treatment steps.
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In particular, Pasloske teaches co-separation of a target nucleic
acid with an internal control, and also suggests that the internal control
may incorporate a liposome. (FF1.) We agree with the Examiner that
an ordinary artisan familiar with the process of centrifugation would
have recognized that, if the liposome-encapsulated nucleic acids of
Pasloske did not pellet (i.e. co-separate) with specific target entities
such as cells or viral particles encapsulating the target nucleic acids of
interest, the nucleic acid-containing liposome standard should be
modified to possess the same density as the target nucleic acid.
Since the methods of Pasloske required co-separation of the
reference and target entities via centrifugation (column 26, lines 32-
38), one of ordinary skill in the art familiar with centrifugation would
have been motivated to ensure that the densities of the target entity and
liposome-encapsulated nucleic acids were as closely matched as
possible. Thus one of ordinary skill in the art would look to known
technology, such as that of Levine, to increase or decrease, or
otherwise modify the density of the liposome particles, using a filler
solution to ensure co-separation of the internal control liposome with
the target nucleic acid. Thus we are not persuaded by Appellants’
arguments.
Appellants provide no additional evidence exemplifying what
was alternatively known to those of ordinary skill in the art.
We adopt the Examiner’s responses to Appellants’ other arguments,
as our own.

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CONCLUSION OF LAW
The Examiner has provided sufficient evidence that it was known in
the prior art to select non-viable liposome particles as an internal control,
having a density, weight, or size which is sufficiently similar to the target
entity to allow co-separation in a density, weight, or size based separation
method, and such that said non-viable liposome particles and said target
entities are able to undergo all of the same treatment steps.

2. Claim 25 is rejected under 35 U.S.C. § 103(a) as being unpatentable
over Pasloske in view of Levine and further in view of Lopez-Saura.

FINDINGS OF FACT
11. Neither Pasloske nor Levine teaches modifying the liposomes to
incorporate polysaccharides such as Blue Dextran or dextran sulfate. (Ans.
10.)
12. Lopez-Saura teaches that Dextran 500 may be used to increase the
density of lysosomes in the purification of hepatoma (HTC) cells (page 430,
step (ii), page 442, and pages 444-445). (Ans. 10.)
13. The Examiner concludes that it would have been prima facie obvious
for one of ordinary skill in the art at the time of invention to apply the
teachings of Lopez-Saura to the method resulting from the combined
teachings of Pasloske and Levine. An ordinary artisan would have been
motivated to increase the density of the liposomes taught by Pasloske using
any known method, such as by incorporating polysaccharides, such as the
Dextran 500, as taught by Lopez-Saura. (Ans. 10-11.)
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14. In this case, Dextran 500 was known in the art to be useful for
increasing the density of a target entity to obtain a desired centrifugation
behavior (see pages 430, 442, 445, and 445 of Lopez-Saura). (Ans. 11.)

ANALYSIS
Appellants argue this rejection by presenting the same arguments as in
the rejection of Pasloske and Levine. (App. Br. 25.) For the reasons given
herein with respect to this combination of references, we affirm this
rejection.

3. Claims 31-34 are rejected under 35 U.S.C. § 103(a) as being
unpatentable over Pasloske in view of Levine and Mader.

FINDINGS OF FACT
15. Pasloske and Levine do not teach that the stability of the liposome
particles is increased by coating with S-layer proteins derived from
thermophilic bacteria or that the liposomes are cationic liposomes. (Ans.
11.)
16. Mader teaches that coating cationic liposomes with an S-layer protein
derived from the thermophilic bacterium, Bacillus stearothermophilus,
increased the stability of the liposomes in the presence of mechanical or
thermal stress (see abstract and pages 111-114). Mader further teaches the
use of cationic liposomes (see abstract and page 107). (Ans. 11-12.)
17. The Examiner concludes that it would have been prima facie obvious
for one of ordinary skill in the art at the time of invention to apply the
teachings of Mader to the method resulting from the combined teachings of
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Pasloske and Levine. An ordinary artisan would have been motivated to
utilize cationic liposomes coated with an S-layer protein derived from a
thermophilic bacterium in this method, because Mader taught that such
liposomes showed an increased stability when subjected to thermal and/or
mechanical stress (see abstract, Figures 2-5, and pages 111-114). (Ans. 12.)
18. The Examiner further concludes that since the method of Pasloske
required co-separation of the target and encapsulated internal control by
centrifugation followed by co-purification of the target and internal control
nucleic acids (see column 25, lines 31-46, column 26, lines 32-38, and
column 43, line 55 - column 44, line 26), an ordinary artisan would have
been motivated to modify the standard-encapsulating entity in order to
match the stability of the target entity, and thereby improve the co-
separation and subsequent co-purification processes. (Ans. 12.)
19. The Examiner concludes that an ordinary artisan would have recognized
that accurate use of the standard taught by Pasloske hinged on reliable co-
separation and co-purification of the encapsulated standard with the target
sequence. Since Mader taught that cationic liposomes coated with an S-layer
protein from a thermophilic organism increased liposome stability (see
abstract), an ordinary practitioner would have been motivated to modify
liposomes in this manner in order to match the stability of internal control-
encapsulating liposomes to the target entities, and thereby, improve the
accuracy of methods depending on reliable co-separation, copurification,
and co-amplification of the IC and target nucleic acids. (Ans. 12.)

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ANALYSIS
Appellants argue this rejection by presenting the same arguments as in
the rejection of Pasloske and Levine. (App. Br. 26.) For the reasons given
herein with respect to this combination of references, we affirm this
rejection.

4. Claims 21 and 31-37 are rejected under 35 U.S.C. § 103(a) as being
unpatentable over Pasloske in view of Levine and further in view of Meyer.

FINDINGS OF FACT
20. Pasloske and Levine do not teach increasing liposome stability by
coating with a hydrophilic polymer such as PEG. These references also do
not teach incorporation of phospholipids derived from PEG in the liposomes.
(Ans. 14.)
21. Pasloske and Levine do not teach that the liposomes are cationic
liposomes comprising one of the neutral lipids POPC or DOPC and one of
the positively charged lipids DDAB, DOTAP or DOSPA. (Ans. 14.)
22. Meyer teaches that cationic liposomes comprised of a cationic lipid
(DOTAP, DDAB or DOGS), a neutral lipid (DOPE) and a phospholipid
derivative of PEG (PEG-PE) showed increased stability relative to
complexes lacking PEG-PE (abstract and Table 1). Note that the use of the
phospholipid derivative PEG-PE results in a coating of the liposome surface
with the hydrophilic polymer PEG. (Ans. 14.)
23. Meyer stated, "Modification of cationic liposomes with PEG-PE
remarkably increased the stability of ODN (oligonucleotide)-liposome
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complexes against aggregation (Table 1) (page 15624, column 2)." (Ans.
14.)
24. The Examiner concludes that it would have been prima facie obvious
for one of ordinary skill in the art at the time of invention to apply the
teachings of Meyer to the method resulting from the combined teachings of
Pasloske and Levine. Since the method of Pasloske required co-separation of
the target and standard-encapsulating entities by centrifugation followed by
co-purification of the target and internal control nucleic acids (see column
26, lines 32-38 and column 25, lines 3 1-46), an ordinary artisan would have
been motivated to modify the standard-encapsulating entity in order to
match the stability of the target entity in order to improve the co-separation
and subsequent co-purification processes. (Ans. 15.)
25. An ordinary artisan would have recognized that accurate use of the
standard taught by Pasloske hinged on the reliable co-separation and co-
purification of the internal control and target entities. Since Meyer taught
that PEG-modified cationic liposomes displayed an increased stability (page
15624), an ordinary artisan would have been motivated to modify liposomes
in this manner in order to match the stability of internal control-
encapsulating liposomes to the target entities, and thereby improve the
accuracy of methods depending on accurate co-separation, co-purification,
and co-amplification of the internal control and target nucleic acids. (Ans.
15.)
26. In this case, Pasloske taught using encapsulated nucleic acids as
internal controls to monitor both the purification and subsequent
amplification steps (column 14, line 29 – column 15, line 55, column 26,
lines 15-39, and column 43, line 55 - column 44, line 26). Pasloske taught a
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specific example utilizing an internal control nucleic acid encapsulated in a
synthetic viral particle (see Example 11, especially column 26, lines 15-39),
and further taught that liposomes could be used to encapsulate the internal
control nucleic acid (column 1 1, lines 32-42 and column 39, lines 14-30),
but did not teach modification of the liposomes to increase their stability.
Meyer taught a method of increasing liposome stability by incorporating
PEG modified phospholipids (page 15624). One of ordinary skill in the art at
the time of invention would have recognized that application of these
teachings of Meyer would have improved the method of Pasloske by
ensuring that the lysis and co-purification steps of the process affected the
target and control entities in the same manner. (Ans. 16.)
27. Application of the teachings of Meyer to the method of Pasloske would
have yielded predictable results and was within the capabilities of the
ordinary artisan. Thus, the methods of claims 21 and 3 1-37 are prima facie
obvious in view of the combined teachings of Pasloske, Levine, and Meyer.
(Ans. 16.)

ANALYSIS
Appellants argue this rejection by presenting the same arguments as in
the rejection of Pasloske and Levine. (App. Br. 27.) For the reasons given
herein with respect to this combination of references, we affirm this
rejection.

5. Claim 42 is rejected under 35 U.S.C. § 103(a) as being unpatentable
over Pasloske in view of Levine and further in view of Pasloske II.

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FINDINGS OF FACT
28. Pasloske I teaches internal control nucleic acids of 1718 bases and 1867
bases (see SEQ ID NO: 3 and SEQ ID NO: 6 described in Example I,
columns 19-22), but does not teach that the encapsulated nucleic acid is 50-
500 bases in length.

29. Pasloske II teaches encapsulated internal control nucleic acids for
monitoring nucleic acid isolation and purification (see abstract, page 3590,
and pages 3593-3594) and teaches that the internal control nucleic acid is
172 nucleotides in length (see Figure 1 and pages 3590-3591). (Ans. 17.)
30. The Examiner concludes that it would have been prima facie obvious
for one of ordinary skill in the art at the time of invention to utilize a nucleic
acid 50-500 nucleotides in length as the encapsulated internal control nucleic
acid when practicing the method resulting from the combined teachings of
Pasloske I and Levine. An ordinary artisan would have been motivated to
utilize a nucleic acid of any useful size as the internal control nucleic acid,
recognizing that the length of the internal control was a matter of design
choice requiring modification according to the identity of the target nucleic
acid. Since Pasloske II taught an encapsulated internal control nucleic acid
that was 172 nucleotides in length, an ordinary artisan would have been
motivated to utilize a nucleic acid control molecule within the claimed range
of 50-500 nucleotides with a reasonable expectation of success. (Ans. 17.)

ANALYSIS
Appellants argue this rejection by presenting the same arguments as in
the rejection of Pasloske and Levine. (App. Br. 27-28.) For the reasons
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given herein with respect to this combination of references, we affirm this
rejection.

All rejections are affirmed. No time period for taking any subsequent
action in connection with this appeal may be extended under 37 C.F.R. §
1.136(a).

AFFIRMED

cdc

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