Ex Parte Hellinga et al

Patent Trial and Appeal Board

Nov 3, 2014

10686529 (P.T.A.B. Nov. 3, 2014)

UNITED STATES PATENT AND TRADEMARK OFFICE
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BEFORE THE PATENT TRIAL AND APPEAL BOARD
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Ex parte HOMME W. HELLINGA and LOREN L. LOOGER1
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Appeal 2012-006246
Application 10/686,529
Technology Center 1600
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Before MELANIE L. McCOLLUM, JEFFREY N. FREDMAN, and
ULRIKE W. JENKS, Administrative Patent Judges.

McCOLLUM, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a
biosensor. The Examiner has rejected the claims for obviousness,
obviousness-type double patenting, indefiniteness, and lacking written
description. We have jurisdiction under 35 U.S.C. § 6(b). We affirm-in-
part.
STATEMENT OF THE CASE
Claims 1, 2, 7–15, 31, 32, and 38–40 are on appeal (App. Br. 2).
Claims 1 and 15 are representative and read as follows:

1 Appellants identify the real party in interest as Duke University (App.
Br. 1).
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1. A biosensor for glucose, which comprises a glucose binding
protein (GBP) and at least one reporter group attached at position 183 of said
GBP, wherein binding of glucose in a glucose-binding pocket of said
biosensor causes a change in signaling by said reporter group.
15. A biosensor for glucose, which comprises a glucose binding
protein (GBP) and at least one reporter group attached at one or more amino
acid positions of said GBP selected from the group consisting of 10, 93 and
183, wherein binding of glucose in a glucose-binding pocket of said
biosensor causes a change in signaling by said reporter group.
Claims 1, 2, 7–15, 31, 32, and 38–40 stand rejected on the ground of
obviousness-type double patenting over claims 1–8 of U.S. Patent
No. 6,277,627 B1 to Hellinga, patented August 21, 2001 (hereinafter
“Hellinga '627”) (Ans. 5).
Claims 1, 2, 7–15, 31, and 32 stand rejected under 35 U.S.C. § 112,
first paragraph, as failing to comply with the written description requirement
(Ans. 5).
Claims 1, 2, 7–15, 31, and 32 stand rejected under 35 U.S.C. § 112,
second paragraph, as being indefinite (Ans. 8).
Claims 1, 2, 7–15, 31, 32, and 38–40 stand rejected under 35 U.S.C.
§ 103(a) as obvious over PCT Publication No. WO 99/34212 A1 to
Hellinga, published July 8, 1999 (hereinafter “Hellinga '212”) (Ans. 9).
Claims 1, 2, 7–15, 31, 32, and 38–40 stand rejected under 35 U.S.C.
§ 103(a) as obvious over Hellinga '627 (Ans. 11).
Claims 1, 2, 7–15, and 38–40 stand rejected under 35 U.S.C. § 103(a)
as obvious over US Publication No. 2003/0134346 A1 to Amiss et al.,
published July 17, 2003 (hereinafter “Amiss '346”) (Ans. 12).
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Claims 1, 2, 7–15, and 38–40 stand rejected under 35 U.S.C. § 103(a)
as obvious over US Patent No. 6,855,556 B2 to Amiss et al., patented
February 15, 2005 (hereinafter “Amiss '556”) (Ans. 13).
INDEFINITENESS
The Examiner finds that claims 1 and 15, respectively, are “rendered
vague and indefinite by the use of [the] term ‘...position 183 of said GBP...’”
and the “phrase ‘...positions of said GBP selected from the group consisting
of 10, 93 and 183[]’” (Ans. 8). In particular, the Examiner finds that,
“[g]iven that there is no base sequence recited in the claim and there are
multiple sequences for GBP known in the art at the time of filing of the
instant application, it is impossible to determine what specific amino acid is
being claimed” (id.).
Appellants argue, however, that “one of skill in the art would
understand what Appellants are claiming when the present claims are read in
light of their specification” (App. Br. 13). In particular, Appellants argue:
[Hellinga '627] is cited by Appellants at page 2, lines 3-6, and
page 57, lines 11-14, of their specification as describing E. coli
periplasmic binding proteins and the amino acid sequence of
GBP, respectively. The contents of the '627 patent are
incorporated by reference on page 57, lines 11-14, of the
present specification.
(Id. at 12.) Appellants also argue that “[o]ne of skill in the art would be able
to align different GBP and identify a position corresponding to positions 10,
93 and 183 of the E. coli GBP as taught in the prior art” (id. at 11).
Findings of Fact
1. The Specification discloses that “Escherichia coli periplasmic
binding proteins are members of a protein superfamily (bacterial periplasmic
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binding proteins, bPBPs) . . . that has been shown to be well suited for the
engineering of biosensors (U.S. Patent 6,277,627)” (Spec. 2: 3-6).
2. The Specification also discloses that “[a]ll documents cited
above are hereby incorporated in their entirety by reference” (id. at 57: 11).
Principles of Law
“[D]uring examination proceedings, claims are given their broadest
reasonable interpretation consistent with the specification.” In re Hyatt, 211
F.3d 1367, 1372 (Fed. Cir. 2000). “[W]hile it is true that claims are to be
interpreted in light of the specification and with a view to ascertaining the
invention, it does not follow that limitations from the specification may be
read into the claims.” Sjolund v. Musland, 847 F.2d 1573, 1581 (Fed. Cir.
1988) (emphasis in original). “[D]uring patent prosecution when claims can
be amended, ambiguities should be recognized, scope and breadth of
language explored, and clarification imposed.” In re Zletz, 893 F.2d 319,
322 (Fed. Cir. 1989).
“[A] claim is not indefinite merely because its scope is not
ascertainable from the face of the claims.” Amgen, Inc. v. Hoechst Marion
Roussel, Inc., 314 F.3d 1313, 1342 (Fed. Cir. 2003). Rather, “[a] claim is
indefinite if, when read in light of the specification, it does not reasonably
apprise those skilled in the art of the scope of the invention.” Id. However,
“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) (precedential).
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Analysis
Appellants’ Specification relies on Hellinga '627, which is
incorporated by reference therein (Finding of Fact (FF) 2), for disclosing
that “Escherichia coli periplasmic binding proteins are members of a protein
superfamily (bacterial periplasmic binding proteins, bPBPs) . . . that has
been shown to be well suited for the engineering of biosensors” (FF 1).
However, we do not agree with Appellants that this teaching makes clear
that the phrases “position 183 of said GBP” and “positions of said GBP
selected from the group consisting of 10, 93 and 183” refer to the alignment
of E. coli GBP. Thus, we agree with the Examiner that these phrases are
indefinite.
Conclusion
The evidence supports the Examiner’s conclusion that claims 1 and 15
are indefinite. We therefore affirm the indefiniteness rejection of claims 1
and 15. Claims 2, 7–14, 31, and 32 have not been separately argued and
therefore fall with claims 1 and 15. 37 C.F.R. § 41.37(c)(1)(vii).
WRITTEN DESCRIPTION
The Examiner finds that, “since no baseline sequence is provided for
. . . the ‘glucose binding protein’ and multiple glucose binding proteins (with
differing sequences) are known in the art, . . . [t]he specification provides
insufficient written description to support the genus encompassed by the
claims” (Ans. 6). In particular, the Examiner finds:
Given that there is no disclosed correlation between the
structure (sequence) of the claimed biosensor and its claimed
function (an alteration in the signaling of the reporter group of
said biosensor due to the binding of glucose in a glucose-
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binding pocket of said biosensor) the requirements of proper
description have not been met.
(Id. at 7.)
Appellants argue, however, that Hellinga '627, which is incorporated
by reference in the present Specification, “is cited for describing E. coli
periplasmic binding proteins, including the amino acid sequence of glucose
binding protein (GBP)” (App. Br. 11). Appellants also argue:
The sequences of GBP from bacteria other than E. coli were
also known in the prior art. . . . One of skill in the art would be
able to align different GBP and identify a position
corresponding to positions 10, 93 and 183 of the E. coli GBP as
taught in the prior art. . . . A specification need not teach, and
preferably omits, what is well known in the art.
(Id.)
Finding of Fact
3. The Specification, as originally filed, claims:
A biosensor for ligand, which comprises a bacterial periplasmic
binding protein (bPBP) which is not maltose binding protein
and at least one reporter group attached at one or more specific
positions of said bPBP; wherein binding of said ligand in a
ligand-binding pocket of said biosensor causes a change in
signaling by said reporter group; with the proviso that a
biosensor comprising a glucose binding protein (GBP) is
limited to attaching at least one reporting group at one or more
positions of said GBP selected from the group consisting of 10,
93, 149 and 183.
(Spec. 58 (claim 1).)
Analysis
On its face, claim 15 recites a reporter group attached at at least one of
positions 10, 93, and 183 of a GBP. Appellants argue that “[o]ne of skill in
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the art would be able to align different GBP and identify a position
corresponding to positions 10, 93 and 183 of the E. coli GBP as taught in the
prior art” (App. Br. 11). However, as discussed above, we do not agree with
Appellants that claim 15 clearly recites that positions 10, 93, and 183 refer to
the alignment of E. coli GBP. Instead, we agree with the Examiner that, as
written, claim 15 can be interpreted to refer to positions 10, 93, and 183 of
each GBP sequence.
We acknowledge that original claim 1 recites a reporter group
attached at at least one of positions 10, 93, 149, and 183 of a GBP (FF 3).
However, we agree with the Examiner that Appellants have not adequately
shown where the Specification describes attaching a reporter group at one or
more of these positions of a GBP having a different sequence than E. coli
GBP would provide the claimed function, that is, a biosensor in which
binding a glucose in the glucose-binding pocket would cause a change in the
signaling by the reporter group.
Conclusion
The evidence supports the Examiner’s conclusion that the
Specification does not provide adequate written description to support
claim 15. We therefore affirm the written description rejection of claim 15.
Claims 1, 2, 7–14, 31, and 32 have not been separately argued and therefore
fall with claim 15. 37 C.F.R. § 41.37(c)(1)(vii).
OBVIOUSNESS - HELLINGA
In rejecting the claims as obvious over each of Hellinga '212 and
Hellinga '627, the Examiner finds that “Hellinga discloses biosensors
comprising glucose binding proteins (GBP) and reporter groups” wherein
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the GBP “include mutations that allow site-specific introduction of the
environmentally sensitive reporter group” (Ans. 9 &11). The Examiner also
finds:
Hellinga further discloses that said reporter groups can be site-
specifically introduced by total synthesis, semi-synthesis or
gene fusion . . . and that a variety of reporter groups can be used
[such as] fluorophores and redox cofactors. . . . Hellinga also
discloses that said reporter groups can be positioned in the
binding pocket (ligand binding pocket) or distally from the
binding pocket. . . . Moreover, Hellinga discloses that the
binding protein can be mutated either within the binding site or
at allosteric sites.
(Id. at 9-10 & 11.)
In addition, the Examiner finds that the “disclosure of Hellinga differs
from the instant invention in that they don’t specifically exemplify the
attachment of the reporter groups to positions 10, 93 or 183 of the glucose
binding protein” (id. at 10 & 11). However, the Examiner finds that
“Hellinga discloses that the strategy for introducing reporter groups into the
exemplified GBP was successfully used with MBP and PBP” (id.). Thus,
the Examiner concludes that “it would have been obvious for the skilled
artisan to utilize any or all of the possible binding sites” (id.).
Appellants argue, however, that each of the Hellinga documents “fails
to teach or make obvious [the] specific position within a GBP for attaching a
reporter group” (App. Br. 14 & 17).
Finding of Fact
4. Each of Hellinga '212 and Hellinga '627 discloses:
The reporter group(s) can be positioned in the binding pocket of
the GBP . . . , so that changes in reporter signal are a
consequence of direct interactions with the bound glucose.
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This approach may be disadvantageous in that it can be
accompanied by unfavorable steric interactions between the
reporter group and glucose which lower the glucose affinity or
substrate selectivity. Alternatively, the reporter group(s) can be
positioned in locations distant from the binding site where the
reporter group(s) senses glucose binding indirectly via an
allosteric coupling mechanism based on detection of the
domain movements. Appropriate allosteric sites are located in
regions of GBP that undergo a local conformational change in
concert with the interdomain bending motion.
(Hellinga '212, 9: 13 to 10: 4; Hellinga '627, col. 4, ll. 21–36.)
Analysis
The Hellinga documents each disclose that the “reporter group(s) can
be positioned in the binding pocket of the GBP” and that, “[a]lternatively,
the reporter group(s) can be positioned in locations distant from the binding
site where the reporter group(s) senses glucose binding indirectly via an
allosteric coupling mechanism based on detection of the domain
movements” (FF 4). However, we conclude that the Examiner has not
adequately shown that it would have been “obvious for the skilled artisan to
utilize any or all of the possible binding sites” (Ans. 21 & 25). In particular,
the Examiner has not provided adequate basis for the conclusion that
attaching a reporter group at a position that is not in the binding pocket or at
an allosteric site would be expected to provide a biosensor in which the
binding of glucose in the glucose-binding pocket causes a change in the
signaling by the reporter group. Therefore, we conclude that the Examiner
has not adequately explained why it would have been obvious to select at
least one of positions 10, 93, and 183.
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Conclusion
The Examiner has not set forth a prima facie case that either
Hellinga '212 or Hellinga '627 teaches or suggests attaching a reporter group
at one or more amino acid positions of GBP selected from the group
consisting of 10, 93, and 183. We therefore reverse the obviousness
rejections over each of Hellinga '212 and Hellinga '627.
OBVIOUSNESS - AMISS
In rejecting the claims as obvious over each of Amiss '346 and
Amiss '556, the Examiner finds:
Amiss et al. disclose biosensors comprising galactose/glucose
binding proteins (GGBP) and reporter groups wherein said
GGBP includes at least on[e] mutation and at least one reporter
group. . . . Amiss et al. further disclose that mutations of
binding proteins include the addition or substitution of cysteine
groups, non-naturally occurring amino acids and replacement of
substantially non-reactive amino acids with reactive amino
acids to provide for the covalent attachment of electrochemical
or photoresponsive reporter groups . . . and that a variety of
reporter groups can be used. . . . Amiss et al. also disclose that
said reporter groups can be attached to the GGBPs by any
conventional means throughout the length of the protein.
(Ans. 12 & 13–14.)
The Examiner also finds that, “while Amiss et al. do not explicitly
disclose the attachment of the reporter group(s) at positions 10, 93 or 183,
Amiss does disclose that said reporter groups can be attached covalently to
cysteine residues” (id. at 12-13 & 14). Thus, the Examiner concludes:
Given that the attachment of reporter groups is well known in
the art yielding predictable results, it is obvious for the skilled
artisan to utilize any or all of the possible binding sites. . . .
Given the success of Amiss attaching a reporter group to
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positions 11, 14, 19, 43, 74, 07, 110, 110, 112, 113, l37, 149,
152, 153, 213, 216, 238, 287 and 292, the skilled artisan would
have had a reasonable expectation of success.
(Id. at 13 & 14.)
Appellants argue, however, that each of the Amiss documents “fails to
teach or make obvious [the] specific position within a GBP for attaching a
reporter group” (App. Br. 19 & 22).
Finding of Fact
5. Each of Amiss '346 and Amiss '556 discloses:
The reporter group may be attached to the mutated protein or
GGBPs by any conventional means known in the art. For
example, the reporter group may be attached via amines or
carboxyl residues on the protein. However, especially preferred
is covalent coupling via thiol groups on cysteine residues. For
example, for mutated GGBP, cysteines located at position 11,
position 14, position 19, position 43, position 74, position 107,
position 110, position 112, position 113, position 137,
position 149, position 152, position 213, position 216,
position 238, position 287, and position 292 are preferred in the
present invention.
(Amiss '346, ¶ 34; Amiss '556, col. 6, l. 65, to col. 7, l. 8 (emphasis
omitted).)
Analysis
The Amiss documents each disclose attaching a reporter group at
various sites (FF 5). However, we conclude that the Examiner has not
adequately shown that it would have been “obvious for the skilled artisan to
utilize any or all of the possible binding sites” (Ans. 28 & 32). In particular,
the Examiner has not provided adequate basis for the conclusion that
attaching a reporter group at “any or all of the possible binding sites” would
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be expected to provide a biosensor in which the binding of glucose in the
glucose-binding pocket causes a change in the signaling by the reporter
group. Therefore, we conclude that the Examiner has not adequately
explained why it would have been obvious to select at least one of positions
10, 93, and 183.
Conclusion
The Examiner has not set forth a prima facie case that either
Amiss '346 or Amiss '556 teaches or suggests attaching a reporter group at
one or more amino acid positions of GBP selected from the group consisting
of 10, 93, and 183. We therefore reverse the obviousness rejections over
each of Amiss '346 and Amiss '556.
DOUBLE PATENTING
The Examiner finds:
Although the conflicting claims are not identical, they are not
patentably distinct from each other because both claims sets are
drawn to biosensors comprising a bPGP and a reporter group
wherein said reporter group is attached to the GBP and can
constitute a fluorophore or a redox cofactor. Moreover, since
the cited patented claims encompass all possible attachment
positions within the GBP and the disclosure of the cited patent
contemplates the same . . . , the specific positions recited in the
instant claims are deemed to be obvious variations of the
patented biosensors.
(Ans. 5.)
Appellants argue, however, that the “Examiner failed to specifically
address how one of ordinary skill in the art would have selected positions
10, 93 and 183 of GBP’s amino acid sequence for attachment of at least one
reporter group with a reasonable expectation of success” (App. Br. 7).
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Findings of Fact
6. Hellinga '627 claims:
A glucose biosensor comprising a glucose binding protein
(GBP) and a reporter group that transduces a detectable signal,
wherein said reporter group is attached to said GBP so that a
signal transduced by said reporter group when said GBP is
bound to glucose differs from a signal transduced by said
reporter group when said GBP is not bound to glucose.
(Hellinga '627, col. 11, l. 54, to col. 12, l. 21 (claim 1).)
7. Hellinga '627 discloses: “Certain aspects of the present
invention are described in greater detail in the non-limiting Examples that
follows. (See also Marvin et al, J. Am. Chem. Soc. 120:7 (1998)).” (Id. at
col. 5, ll. 57-60.)
8. The Specification discloses that position 183 is endosteric
(Spec. 35 & 44), that is, “it interacts directly with the ligand” (id. at 7: 26-
28).
Analysis
Claim 1 of Hellinga '627 “encompasses all possible attachment
positions within the GBP” at which a signal transduced by the reporter group
when the GBP is bound to glucose differs from a signal transduced by the
reporter group when the GBP is not bound to glucose (Ans. 5). However,
for the reasons discussed above, the Examiner has not shown that
Hellinga '627 suggests that positions 10, 93, and 183 are positions at which a
signal transduced by the reporter group when the GBP is bound to glucose
differs from a signal transduced by the reporter group when the GBP is not
bound to glucose.
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The Examiner responds that the specification of Hellinga '627 “also
discloses (via the Marvin et al. reference) the means of selecting positions
for reporter groups (fluorophores) [see column 5, line 59]” (Ans. 15). We
note that Hellinga '627 refers to at least one Marvin et al. reference (FF 7).
However, the Examiner does not reject the claims in view of this reference.
Therefore, we decline to consider whether this reference suggests positions
10, 93, and 183.
The Examiner also responds “that residue 183 resides within the
ligand binding pocket” (Ans. 15). We note that the Specification does
disclose that residue 183 is endosteric, that is, “it interacts directly with the
ligand” (FF 8). However, the Examiner has not demonstrated that this was
known in the art at the time of the present invention. Therefore, we
conclude that the Examiner has not adequately explained why it would have
been obvious to select at least one of positions 10, 93, and 183.
Conclusion
The Examiner has not set forth a prima facie case that claims 1–8 of
Hellinga '627 suggest attaching a reporter group at one or more amino acid
positions of GBP selected from the group consisting of 10, 93, and 183. We
therefore reverse the obviousness-type double patenting rejection.
SUMMARY
We affirm the rejections of claims 1, 2, 7–15, 31, and 32 under
35 U.S.C. § 112, first and second paragraphs. However, we reverse the
obviousness and obviousness-type double patenting rejections. Thus,
claims 38–40 are not currently subject to a rejection.
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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).

AFFIRMED-IN-PART

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