Ex Parte Nakanishi et al

Board of Patent Appeals and Interferences

Oct 20, 2009

10149450 (B.P.A.I. Oct. 20, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte KAZOU NAKANISHI, YOSHIMI KIKUCHI, JUNICHIRO
KOJIMA, TOMOKO SUZUKI, YASUSHI NISHIMURA,
and HIROYUKI KOJIMA
__________

Appeal 2009-000292
Application 10/149,450
Technology Center 1600
__________

Decided: October 20, 2009
__________

Before TONI R. SCHEINER, DEMETRA J. MILLS, and STEPHEN
WALSH, Administrative Patent Judges.

MILLS, Administrative Patent Judge.

DECISION ON APPEAL

This is an appeal under 35 U.S.C. § 134. The Examiner has rejected
the claims as indefinite and as lacking descriptive support. We have
jurisdiction under 35 U.S.C. § 6(b).
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STATEMENT OF THE CASE
Claims 28-32 and 39-42, which are all the pending claims, stand
rejected by the Examiner under 35 U.S.C. § 112, first and second paragraphs.
Claims 21 and 26 are listed below to provide an antecedent basis for
the pending dependent claims. (Bracketed claims are provided to provide
antecedent basis for pending dependent claims.)

The following claims are representative and read as follows:

[21. An Escherichia coli bacterium in which:
(a) the intracellular activities of all of the following enzymes are
enhanced:
dihydrodipicolinate synthase,
aspartokinase,
dihydrodipicolinate reductase,
phosphoenolpyruvate carboxylase,
nicotinamide adenine dinucleotide transhydrogenase, and
aspartate-semialdehyde dehydrogenase; and
(b) the intracellular activities of at least one of the following enzymes are
enhanced:
i) diaminopimelate dehydrogenase, or
ii) tetrahydrodipicolinate succinylase and succinyldiaminopimelate
deacylase, wherein said activities are enhanced by a method selected from
the group consisting of a) introducing a promoter or promoters which are
operably linked to the gene encoding the enzymes into the chromosome of
said bacterium,
b) by increasing the copy number of the genes encoding the enzymes
by introducing one or more expression vectors into said bacterium, and
c) combinations thereof.

26. An Escherichia coli bacterium comprising one or more expression
vectors comprising
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(a) genes encoding all of the following:
dihydrodipicolinate synthase,
aspartokinase,
dihydrodipicolinate reductase,
phosphoenolpyruvate carboxylase,
nicotinamide adenine dinucleotide transhydrogenase, and
aspartate-semialdehyde dehydrogenase, and
(b) a gene encoding at least one of the following:
i) diaminopimelate dehydrogenase, or
ii) tetrahydrodipicolinate succinylase and succinyldiaminopimelate
deacylase.]

28. The bacterium of claim 21, wherein said dihydrodipicolinate synthase
comprises a mutation replacing at least one amino acid selected from the
group consisting of the 81st alanine and the 118th histidine with another
amino acid in the amino acid sequence of the wild-type dihydrodipicolinate
synthase of Escherichia coli.

29. The bacterium according to claim 21, wherein said aspartokinase
comprises a mutation selected from the group consisting of:
(a) replacement of 323rd glycine with another amino acid,
(b) replacement of 323rd glycine and 408th glycine with another amino
acid,
(c) replacement of 34th arginine and 323rd glycine with another amino
acid,
(d) replacement of 325th leucine with another amino acid,
(e) replacement of 318th methionine with another amino acid,
(f) replacement of 318th methionine and 349th valine with another amino
acid,
(g) replacement of 345th serine with another amino acid,
(h) replacement of 347th valine with another amino acid,
(i) replacement of 352nd threonine with another amino acid,
(j) replacement of 352nd threonine and 369th serine with another amino
acid,
(k) replacement of 164th glutamine with another amino acid,
(1) replacement of 417th methionine and 419th cysteine with another
amino acid,
(m) replacement of 323rd glycine and 318th methionine with another amino
acid, and
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(n) combinations thereof,
in the amino acid sequence of the wild-type aspartokinase III of Escherichia
coli.

30. The bacterium of claim 26, wherein said dihydrodipicolinate synthase
comprises a mutation replacing at least one amino acid selected from the
group consisting of 81st alanine and 118th histidine with another amino acid
in the amino acid sequence of the wild-type dihydrodipicolinate synthase of
Escherichia coli.

31. The bacterium of claim 26, wherein said aspartokinase comprises a
mutation selected from the group consisting of:
(a) replacement of 323rd glycine with another amino acid,
(b) replacement of 323rd glycine and 408th glycine with another amino
acid,
(c) replacement of 34th arginine and 323rd glycine with another amino
acid,
(d) replacement of 325th leucine with another amino acid,
(e) replacement of 318th methionine with another amino acid,
(f) replacement of 318th methionine and 349th valine with another amino
acid,
(g) replacement of 345th serine with another amino acid,
(h) replacement of 347th valine with another amino acid,
(i) replacement of 352nd threonine with another amino acid,
(j) replacement of 352nd threonine and 369th serine with another amino
acid,
(k) replacement of 164th glutamate with another amino acid,
(1) replacement of 417th methionine and 419th cysteine with another
amino acid,
(m) replacement of 323rd glycine and 318th methionine with another
amino acid, and
(n) combinations thereof,
in the amino acid sequence of the wild-type aspartokinase III of Escherichia
coli.

39. A method of producing L-lysine comprising culturing the bacterium
of claim 28 in a medium, allowing L-lysine to accumulate, and collecting L-
lysine from the culture.
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40. A method of producing L-lysine comprising culturing the bacterium
of claim 29 in a medium, allowing L-lysine to accumulate, and collecting L-
lysine from the culture.

41. A method of producing L-lysine comprising culturing the bacterium
of claim 30 in a medium, allowing L-lysine to accumulate, and collecting L-
lysine from the culture.

42. A method of producing L-lysine comprising culturing the bacterium
of claim 31 in a medium, allowing L-lysine to accumulate, and collecting L-
lysine from the culture.

Cited References
None cited

Grounds of Rejection
1. Claims 28-31 and 39-42 are rejected under 35 U.S.C. 112, second
paragraph, as failing to set forth the subject matter, which applicant(s) regard
as their invention. (Answer 5.)

2. Claims 28-31 and 39-42 are rejected under 35 U.S.C. 112, first
paragraph, as containing subject matter which was not described in the
specification in such a way as to reasonably convey to one skilled in the
relevant art that the inventor(s), at the time the application was filed, had
possession of the claimed invention. (Answer 2-3.)

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Indefiniteness
1. Claims 28-31 and 39-42 are rejected under 35 U.S.C. 112, second
paragraph, as failing to set forth the subject matter, which applicant(s) regard
as their invention. (Answer 5.)
The Examiner contends that “[c]laims 28-31 and their dependent
claims are indefinite for the recitation of ‘amino acid positions’ absent a
specific sequence/structure, because it is unclear what structure the specific
amino acid position corresponds to.” Id.
Appellants contend that the phrases ‘“the amino acid sequence of the
wild-type dihydrodipicolinate synthase of Escherichia coli’ and “‘in the
amino acid sequence of the wild-type aspartokinase III of Escherichia coli”’
clearly provide a specific structure as to the amino acids which are referred
to in the claims, as these are known sequences in the prior art and are not
required to be recited in the claims or the specification. (Appeal Br. 13.)
The issue is: Have Appellants demonstrated error in the Examiner’s
indefiniteness rejection?

PRINCIPLES OF LAW
Claim Interpretation
Claim construction presents a question of law that courts review de
novo. Compare Cybor Corp. v. FAS Techs., Inc., 138 F.3d 1448, 1456 (Fed.
Cir. 1998) and In re American Academy Of Science Tech Center, 367 F.3d
1359, 1363 (Fed. Cir. 2004). Unlike in post-issuance claim construction, the
USPTO gives pending claims “their broadest reasonable interpretation
consistent with the specification” and “in light of the specification as it
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would be interpreted by one of ordinary skill in the art.” In re Am. Acad. of
Sci. Tech. Ctr., 367 F.3d 1359, 1364 (Fed. Cir. 2004). This broader claim
construction standard is justified because, during prosecution, the applicant
has the opportunity to amend the claims, and the Federal Circuit has held
that an applicant has the opportunity and the obligation to define his or her
invention precisely during proceedings before the USPTO. See In re Morris,
127 F.3d 1048, 1056-57 (Fed. Cir. 1997) (35 U.S.C. § 112, second
paragraph, places the burden of precise claim drafting on the applicant); In
re Zletz, 893 F.2d 319, 322 (Fed. Cir. 1989) (manner of claim interpretation
that is used by courts in litigation is not the manner of claim interpretation
that is applicable during prosecution of a pending application before the
USPTO). “An essential purpose of patent examination is to fashion claims
that are precise, clear, correct, and unambiguous. Only in this way can
uncertainties of claim scope be removed, as much as possible, during the
administrative process.” Id.

Indefiniteness
One of the purposes of 35 U.S.C. § 112, second paragraph, “is to
provide those who would endeavor, in future enterprise, to approach the area
circumscribed by the claims of a patent, with the adequate notice demanded
by due process of law, so that they may more readily and accurately
determine the boundaries of protection involved and evaluate the possibility
of infringement and dominance.” In re Hammack , 427 F.2d 1378, 1382
(CCPA 1970) (citations omitted). As set forth in Amgen Inc. v. Chugai
Pharmaceutical Co., Ltd., 927 F.2d 1200, 1217 (Fed. Cir. 1991):
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The statute requires that “[t]he specification shall conclude with
one or more claims particularly pointing out and distinctly claiming
the subject matter which the applicant regards as his invention.” A
decision as to whether a claim is invalid under this provision requires
a determination whether those skilled in the art would understand
what is claimed. See Shatterproof Glass Corp. v. Libbey-Owens Ford
Co. , 758 F.2d 613, 624, 225 USPQ 634, 641 (Fed. Cir. 1985) (Claims
must “reasonably apprise those skilled in the art” as to their scope and
be “as precise as the subject matter permits.”).

Furthermore, claim language “must be analyzed not in a vacuum, but
always in light of the teachings of the prior art and of the particular
application disclosure as it would be interpreted by one possessing the
ordinary level of skill in the pertinent art.” In re Moore, 439 F.2d 1232,
1235, 169 USPQ 236, 238 (CCPA 1971).
Also, during prosecution “if a claim is amenable to two or more
plausible claim constructions, the USPTO is justified in requiring the
applicant to more precisely define the metes and bounds of the claimed
invention by holding the claim unpatentable under 35 U.S.C. § 112, second
paragraph, as indefinite.” Ex Parte Miyazaki, 89 USPQ2d 1207, 1211 (BPAI
2008). “[A]mbiguity in claim scope is at the heart of the definiteness
requirement of 35 U.S.C. § 112, ¶ 2.” Amgen, Inc. v. Hoechst Marion
Roussel, Inc., 314 F.3d 1313, 1342, 65 USPQ2d 1385, 1406 (Fed. Cir.
2003).

ANALYSIS
This rejection turns on claim interpretation. Claim 28 recites, “The
bacterium of claim 21, wherein said dihydrodipicolinate synthase comprises
a mutation replacing at least one amino acid selected from the group
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consisting of the 81st alanine and the 118th histidine with another amino acid
in the amino acid sequence of the wild-type dihydrodipicolinate synthase of
Escherichia coli.”
Without a reference to a specific wild-type dihydrodipicolinate
synthase sequence, we are unable to discern the meaning of claim 28 and
other dependent claims with similar recitations, or the scope of the subject
matter which appellant regards as his invention. We agree with the
Examiner that a person of ordinary skill would need some standard by which
to identify the numbered amino acids and the respective sequences claimed.
Appellants did not show that a person of ordinary skill could have resolved
the deficit by reliance on either teachings of the prior art or the
Specification. See Moore, 439 F.2d at 1235.
Further, in our view, claim 28 has two possible meanings to one of
ordinary skill in the art. Claim 28 can refer to either an alanine at the 81st
position of wild-type dihydrodipicolinate synthase of Escherichia coli, or
alternatively, to the 81st alanine in the wild-type dihydrodipicolinate
synthase sequence. Because the claims as read by one of ordinary skill in
the art are subject to two different, reasonable meanings, the claims are
indefinite. Ex Parte Miyazaki, 89 USPQ2d 1207, 1211 (BPAI 2008).

CONCLUSION OF LAW
Appellants have not demonstrated with appropriate evidence that the
Examiner’s indefiniteness rejection is in error. The indefiniteness rejection
is affirmed.

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Written Description
2. Claims 28-31 and 39-42 are rejected under 35 U.S.C. 112, first
paragraph, as containing subject matter which was not described in the
specification in such a way as to reasonably convey to one skilled in the
relevant art that the inventor(s), at the time the application was filed, had
possession of the claimed invention. (Answer 3.)
ISSUE
The Examiner finds that the Specification does not disclose the wild
type amino acid sequence of enzymes such as dihydrodipicolinate synthase
(DDPS) and aspartokinase III (AKIII) sequences, and that even though the
Specification mentions specific sequence variations from wild-type, the lack
of recitation of the original wild type sequences demonstrates lack of
description and lack of possession of the claimed invention.
Appellants contend that the claimed wild type sequences are known in
the art and that what is known in the art is not required to be recited in the
specification.
The issues are: Have Appellants demonstrated error in the
Examiner’s written description rejection? Does the Specification need to
recite what is well known in the art and essential to the claimed invention?

FINDINGS OF FACT
1. The claimed invention is directed to an Escherichia coli bacterium
having enhanced intracellular activities of enzymes such as
dihydrodipicolinate synthase (DDPS) and aspartokinase III (AKIII)
wherein said enzymes comprise sequence variations compared to the
wild type. (Answer 3.)
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2. The Examiner finds that claims 28-31 recite amino acid sequence
variations of DDPS without a reference structure and the recited wild-
type language is insufficient as the chemical structure being modified
is missing from the claim. For example, the claimed invention
includes aspartokinase comprising sequence variations (i.e.
replacement of Gly 323). (Answer 3.)
3. The Specification does not disclose specific reference wild type
sequences of enzymes such as dihydrodipicolinate synthase (DDPS)
and aspartokinase III (AKIII) sequences.
4. The Specification, page 12, points to a foreign document as an
example of a DDPS which bears essential subject matter based on the
recitation of “wild-type” in the claims. (Answer 6.)
5. The Examiner finds that the meaning of “wild-type” “is not fixed.
There maybe a sequence disclosed in the foreign document, but
whether it is the true wild-type is anyone's guess. In any population of
organism there is much sequence variation, so what then is the ‘wild-
type.’ Moreover, bacteria have many strains” and thus it is unclear
which wild-type strain is referenced. (Answer 6.)
6. According to the Examiner, the Specification, pages 12-13, 15, 17, 18
and 23-25 list sequence notations, however, the instant specification
mentions that the sequence can be found in a foreign application,
which represents improper incorporation by reference. (Answer 3.)
7. The Examiner finds that the skilled artisan cannot envision the
detailed chemical structure of the enzymes to demonstrate possession
of the invention. (Answer 3.)
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8. The Specification indicates that “the expression of ‘intracellular
activity is enhanced’ means that the intracellular enzymatic activity is
increased compared with a wild strain (for example, E. coli W3110
strain) or a parent strain (strain in which intracellular activities of all
the enzymes included in the combinations specified in the present
invention are not enhanced), and also means that a bacterium has an
enzymatic activity that is not possessed by a wild stain or a parent
strain.” (Specification 8-9.) The Specification and Appellants
provide no evidence that references or known publications disclosed
the sequences of the E coli W3110 strain.
9. The Specification states:
An aspartokinase gene (lysC) can be obtained by amplification by
PCR using E. coli chromosome DNA as a template and two kinds of
oligonucleotide primers prepared based on the known nucleotide
sequence of lysC (Cassan, M., Parsot, C., Cohen, G.N., and Patte,
J.C., J. Biol. Chem., 261, 1052 (1986) (for example, those mentioned
in International Publication No. W095/16042, SEQ ID NOS: 5 and 6).
An aspartate-semialdehyde dehydrogenase gene (asd) can be
obtained from the plasmid pAD20 (Haziza, C. et al., EMBO, 1, 379
(1982)), which contains this gene. If pAD20 is digested with AseI and
ClaI, a DNA fragment containing asd will be obtained.
A dihydrodipicolinate synthase gene (dapA) can be obtained by
amplification by PCR using E . coli chromosome DNA as a template
and two kinds of oligonucleotide primers (for example, those of SEQ
ID NOS: 1 and 2 mentioned in International Publication No.
W095/16042) prepared based on the known nucleotide sequence of
dapA (Richaud, F. et al., J. Bacteriol., 297 (1986)).
A dihydrodipicolinate reductase gene (dapB) can be obtained
by amplification by PCR using E. coli chromosome DNA as a
template and two kinds of oligonucleotide primers (for example, those
of SEQ ID NOS: 9 and 10 mentioned in International publication No.
W095/16042).

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(Specification 12.)

The Specification does not refer to these strains as wild-type
strains.
11. The Specification references an E. coli F15 strain but does not refer to
this strain as a wild-type strain. The Specification describes E.coli K-
12, JM109, and AJ12929 strains but does not refer to these strains as
wild-type strains. (Specification 11, 14.)

PRINCIPLES OF LAW
“The ‘written description’ requirement . . . serves both to satisfy the
inventor’s obligation to disclose the technologic knowledge upon which the
patent is based, and to demonstrate that the patentee was in possession of the
invention that is claimed. . . . The descriptive text needed to meet these
requirements varies with the nature and scope of the invention at issue, and
with the scientific and technologic knowledge already in existence.” Capon
v. Eshhar, 418 F.3d 1349, 1357 (Fed. Cir. 2005). The purpose of the written
description requirement “is to ensure that the scope of the right to exclude …
does not overreach the scope of the inventor's contribution to the field of art
as described in the patent specification.” Reiffin v. Microsoft Corp., 214 F.3d
1342, 1345-46 (Fed. Cir. 2000). The goal of the written description
requirement is “to clearly convey the information that an applicant has
invented the subject matter which is claimed.” In re Barker, 559 F.2d 588,
592 n.4 (CCPA 1977)
"A disclosure in an application, to be complete, must contain such
description and details as to enable any person skilled in the art or science to
which the invention pertains to make and use the invention as of its filing
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date.” In re Glass, 492 F.2d 1228, 1232 (CCPA 1974). A claim which
omits matter disclosed to be essential to the invention as described in the
specification or in other statements of record may also be subject to rejection
under 35 U.S.C. 112, para. 1, as not enabling, or under 35 U.S.C. 112, para.
2. In re Collier, 397 F.2d 1003 (CCPA 1968).
‘“Essential material”’ to an application is defined as “that which is
necessary to (1) support the claims, or (2) for adequate disclosure of the
invention (35 U.S.C. § 112).”’ M.P.E.P. § 608.01(p)(B), at 600-35 (1983).
Quaker City Gear Works, Inc. et al. v. Skil Corporation, 747 F.2d 1446,
1455 n. 10 (Fed. Cir. 1984).

ANALYSIS
Appellants contend that the claimed wild type sequences are known in
the art and reported in the literature and that what is known in the art is not
required to be recited in the Specification. (Appeal Br. 9-10.) Appellants
argue that incorporation of known material into the Specification is
unnecessary. (Appeal Br.10.)
The Examiner finds that the Specification does not disclose the wild
type sequence of enzymes such as dihydrodipicolinate synthase (DDPS) and
aspartokinase III (AKIII) sequences, and that even though the Specification
mentions specific sequence variations from wild-type, the lack of recitation
of the original wild type sequences demonstrates lack of description and lack
of possession of the claimed invention.
Appellants rely on Capon v. Eshhar, 418 F.3d 1349, 1359 (Fed. Cir.
2005) and Falko-Gunter Falkner v. Inglis, 448 F.3d 1357, 1363 (Fed. Cir.
2006) in support of written description in the present case and argue that
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these cases are directly on point to the issue before us. (Appeal Br. 11.)
Appellants argue that these cases stand for the proposition that one does not
need to describe in a patent application that which is known in the prior art
to comply with the written description requirement. (Appeal Br. 11.)
We find the facts of the present case distinguishable from those of
both Capon and Falkner, and are not persuaded that Appellants provided an
evidentiary showing similar to Capon or Falkner. In Capon the claims were
directed to a chimeric DNA encoding a membrane bound protein. In Capon,
“[b]oth Eshhar and Capon explain[ed] that [their] invention does not concern
the discovery of gene function or structure, as in Lilly. The chimeric genes
here at issue are prepared from known DNA sequences of known function.”
Capon at 1358. In Capon, evidence of record and Declaration evidence
showed that the relevant DNA was known in the prior art.
Unlike Capon, the present claims claim variations in structure based
on an unreferenced wild-type of an E.coli species strain. While Appellants
argue that such sequences are known in the art and provided in foreign
publications, unlike Capon, Appellants have not provided any evidence to
support such argument and do not indicate which specific sequences
disclosed in these foreign publications contain the relevant wild-type
sequence. The Specification does not disclose a specific reference to wild
type sequences of enzymes such as dihydrodipicolinate synthase (DDPS)
and aspartokinase III (AKIII) sequences. While the Specification makes
reference to several publications disclosing dihydrodipicolinate synthase
(DDPS) and aspartokinase III (AKIII) sequences there is no indication that
these are wild-type sequences. The Examiner noted that the meaning of
“wild-type” is not fixed in the context of the present claim, but may
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encompass several different E. coli strains. For this reason, one of ordinary
skill in the art is unable to determine which wild-type E.coli strain is
referenced and encompassed by the claim, and the scope of the claims
becomes unclear in the context of the dependent claims reciting specific
alterations in an E. coli “wild-type” strain which is not of record.
In Falkner, the claims were directed to a vaccine including a mutant
(defective) poxvirus. Falkner argued that, in an interference context, Inglis
did not describe the poxvirus of the invention. The Board found that
evidence of publications in professional journals disclosed the DNA
sequence of the poxvirus genome along with the locations of the essential
regions of these viruses. The Federal Circuit did not find error in the
Board’s finding that, for priority purposes, the absence of incorporation by
reference to prior art publications disclosing the poxvirus in the Inglis
application was not problematic, because of the ready accessibility of the
journals. Falkner at 1366.
In contrast, in the present case Appellants have pointed to no specific
evidence in the prior art of an E.coli strain as in the dependent claims having
specific amino acids at specific numerical locations. Nor do the SEQ ID’s
of record recite such sequences. Appellants provided no evidence that
relevant sequences were known in the art, and rely simply on attorney
arguments that sequences are known in the art. In the absence of evidence
supporting these arguments, we find that Appellants have not rebutted the
Examiner’s finding of prima facie lack of description. See Hyatt v. Doll,
576 F.3d 1246, 1279 (Fed. Cir. 2009) (in the absence of evidence pertinent
to missing source code features, attorney argument was insufficient to rebut
the written description rejection).
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The purpose of the written description requirement “is to ensure that
the scope of the right to exclude… does not overreach the scope of the
inventor's contribution to the field of art as described in the patent
specification.” Reiffin v. Microsoft Corp., 214 F.3d 1342, 1345-46 (Fed.
Cir. 2000). In the present case, we are unable to determine the scope of the
inventor’s contribution as the scope of the claim is unclear for the reasons
herein.
CONCLUSION OF LAW
Appellants have not demonstrated error in the Examiner’s written
description rejection.
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

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