Ex Parte Sode et al

Patent Trial and Appeal Board

Aug 24, 2016

13282243 (P.T.A.B. Aug. 24, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/282,243 10/26/2011
9629 7590 08/26/2016
MORGAN LEWIS & BOCKIUS LLP (WA)
1111 PENNSYLVANIA A VENUE NW
WASHINGTON, DC 20004
FIRST NAMED INVENTOR
Koji Sode
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www .uspto.gov
ATTORNEY DOCKET NO. CONFIRMATION NO.
068022-5136 5411
EXAMINER
STEADMAN, DAVID J
ART UNIT PAPER NUMBER
1656
NOTIFICATION DATE DELIVERY MODE
08/26/2016 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address( es):
patents@morganlewis.com
karen.catalano@morganlewis.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte KOJI SODE and KA TSUHIRO KOJIMA
Appeal2014-007206
Application 13/282,243 1
Technology Center 1600
Before ULRIKE W. JENKS, JACQUELINE T. HARLOW, and
RYAN H. FLAX, Administrative Patent Judges.
FLAX, Administrative Patent Judge.
DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. § 134(a) involving
claims directed to an isolated mutant glucose dehydrogenase with improved
specificity. Claims 1-3, 8-11, 15, 16, 18, and 19 are on appeal as rejected
under 35 U.S.C. §§ 102(b) and 103(a), and under the doctrine of
obviousness-type double patenting. We have jurisdiction under 35 U.S.C.
§ 6(b ).
We affirm.
1 The Real Parties in Interest are ARKRA Y, INC. and Bioengineering
Laboratories, LLC. Br. 1.
Appeal2014-007206
Application 13/282,243
STATEMENT OF THE CASE
The Specification describes a mutant glucose dehydrogenase (GDH)
having increased substrate specificity, meaning it is more sensitive to
glucose relative to maltose. Spec. i-f 1. GDHs are useful for glucose sensors
and the problem addressed by the invention is that such sensors are
incapable of accurately measuring the blood sugar (glucose) level where
blood maltose is high because of high sensitivity to maltose. Id. i-fi-1 1-2. A
mutant enzyme of CyGDH (a GDH used for blood glucose sensors and
comprising a mutant-type a-subunit that constitutes a cytochrome C-
containing GDH) having mutations at its 326th and 365th amino acid residues
where glutamine (Q) and tyrosine (Y) are substituted, respectively (referred
to as CyGDH(QY)) is known to mitigate the influence of maltose in blood
glucose testing. Id. i-fi-1 1--4. The invention seeks to improve upon this by
introducing an additional mutation at position 4 72 by replacing the
respective amino acid with tyrosine (Y). Id. i-f 6.
The appealed claims can be found in the Claims Appendix of the
Appeal Brief. Claim 1 is the sole independent claim, is representative, and
reads as follows:
1. An isolated mutant glucose dehydrogenase comprising an
amino acid sequence at least 80% identical to the amino acid
sequence of SEQ ID N0:3 and having glucose dehydrogenase
activity,
wherein amino acid residues of the mutant glucose
dehydrogenase corresponding to positions 326, 365 and 472 of
SEQ ID N0:3 are replaced with glutamine, tyrosine and tyrosine,
respectively,
wherein said mutant glucose dehydrogenase shows an increased
substrate specificity to glucose and a reduced reactivity to
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Application 13/282,243
disaccharides as compared to a wild-type glucose dehydrogenase
having the amino acid sequence of SEQ ID NO: 3.
Br. 18 (Claims App'x).
The following rejections are on appeal:
Claims 1-3, 8-11, 15, 16, 18, and 192 rejected under 35 U.S.C.
§ 102(b) as anticipated by Yamaoka 833. 3 Final Action 10.
Claims 1-3, 8-11, 15, 16, 18, and 19 rejected under 35 U.S.C.
§ 103(a) over Sode4 and Yamaoka 833. Final Action 14.
Claims 1-3, 8-11, 15, 16, 18, and 19 rejected under the judicially
created doctrine of obviousness-type double patenting as unpatentable over
claims 1, 3-8, 11, 13, 15, and 20-25 of Yamaoka 969. 5 Final Action 21.
Claims 1-3, 8-11, 15, 16, 18, and 19 rejected under the judicially
created doctrine of obviousness-type double patenting as unpatentable over
claims 1 and 4--10 of Yamaoka 5296 in view of Yamaoka 833. Final Action
'"'IL
LU.
2 Claims 21-24 are cancelled by Appellants. Br. 20 (Claims App'x).
3 U.S. Patent Application Pub. No. 2008/0206833 (published Aug. 28, 2008)
(hereinafter "Yamaoka 833").
4 U.S. Patent No. US 7,741,090 B2 to Sode (issued June 22, 2010)
(hereinafter "Sode").
5 U.S. Patent No. US 7,604,969 B2 to Yamaoka et al. (issued Oct. 20, 2009)
(hereafter "Yamaoka 969").
6 U.S. Patent No. US 7,803,592 B2 to Yamaoka (issued Sept. 28, 2010)
(hereafter "Yamaoka 592").
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Application 13/282,243
FINDINGS OF FACT
Except where otherwise noted, we adopt the Examiner's findings of
fact, reasoning on scope and content of the prior art, and conclusions set out
in the Final Action and Answer. We identify the following only to highlight
certain facts.
FF 1. Yamaoka 833 disclosed:
The mutant GDH of the present invention shows improved
substrate specificity to glucose, because it is obtained by adding
the specific mutation to such a wild type GDH or GDH having a
conservative mutation as described above. The "improved
substrate specificity to glucose" include reduced reactivity to
other monosaccharides, disaccharides and oligosaccharides such
as maltose, galactose and xylose with the substantially same
reactivity to glucose, and improved reactivity to glucose
compared with reactivities to other saccharides. For example,
even if the reactivity to glucose is reduced, if the reactivities to
other saccharides are reduced in larger degrees, the substrate
specificity for glucose is improved.
Yamaoka 833 i-f 32.
FF2. Yamaoka 833 disclosed:
Specific examples of the specific mutation include the
followings ....
(2) Substitution of another amino acid residue for the amino acid
residue at a position corresponding to the 365th position of the
amino acid sequence of SEQ ID NO: 3, and substitution of
another or other amino acid residues for at least one or arbitrary
two or more amino acid residues at position or positions
corresponding to the 324th, 326th, 333rd, 334th, 368th, 369th,
376th, 377th, 418th, 419th, 436th, 433rd, 448th, 472nd, 475th,
525th and 529th positions in the amino acid sequence of SEQ ID
N0:3 ...
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Application 13/282,243
Examples of the other amino acid residue mentioned in the above
mutation [at position 365] include those of amino acids other
than serine, . . . [a ]mong these, residues of phenylalanine,
tyrosine, tryptophan and histidine are preferred ....
Among the aforementioned positions of the amino acid
substitution, the 326th position, the 472nd position, the 475th
position, and the 529th position are preferred ...
The amino acid residue after the substitution at the 4 72nd
position is preferably aspartic acid, glutamic acid, phenylalanine,
tyrosine, isoleucine, asparagine or histidine residue, particularly
preferably aspartic acid residue ....
The amino acid residue after the substitution at the 326th position
is preferably glutamine or valine residue.
Yamaoka 833 i-fi-134--40, claims 1, 6, 8, and 16; see also Final Action 10-11
and Ans. 17-18 (discussing Yamaoka).
FF3. Yamaoka 833-disclosed SEQ ID NO: 3 is 100% identical to
SEQ ID NO: 3 of the appealed claims. Final Action 10 (referencing App'x
to Office Action dated Mar. 9, 2012).
FF4. Yamaoka 833 disclosed, "it was estimated that the 365th
position was a very effective position for reducing the reactivity to maltose.
Therefore, it was decided to examine this position in detail." Yamaoka 833
i180; see also Final Action 10-21 and Ans. 5-14 (discussing Yamaoka 833).
FF5. Yamaoka 833 disclosed replacing the amino acid at position
365 of SEQ ID NO: 3 with tyrosine. Id. table 15; see also Final Action 10-
21 and Ans. 5-14 (discussing Yamaoka 833).
FF6. Yamaoka 833 disclosed, "[ t ]he specific activity for glucose,
specific activity for maltose and reaction ratio (specific activity for
maltose/specific activity for glucose, unit is U/ml.) of each mutant GDH are
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Application 13/282,243
shown in Table 16. As for the substrate concentration, the evaluation was
performed at 5 mM and 10 mM." Yamaoka 833 i-f 84; see also Final Action
10-21 and Ans. 5-14 (discussing Yamaoka 833). An excerpt of Table 16 is
reproduced below:
\Vild
type
Single mutagenesis U/ml (culture medium)
5 mivi 10m~1
Glucose Maltose Mal/Glc Glucose Maltose Mal/Ole
2.87 0.77 16 90/ kt ~ /0 2.52 1 ')') .~ ...
***
S365Y 1.42 0.02 1.6% 2.46 0.05
Table 16 (in excerpt) shows that wild type GDH coded by SEQ ID NO: 3
had a maltose/glucose specific activity reaction ratio of 26.9% and 48.2% at
5mM and lOmM, but when tyrosine was substituted at the 365 position these
ratios decreased to 1.6% and 2.0% respectively, indicating improved
specificity for glucose respective of maltose. Id. i-f 85.
FF7. Yamaoka 833, based on the aforementioned results shown at
Table 16, disclosed:
it became clear that the 365th position was an extremely highly
effective position for improving the substrate characteristics.
Therefore, aiming at further improvement of the substrate
characteristics by combining the amino acid substitution at the
3 65th position and amino acid substitutions at other positions,
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Application 13/282,243
further studies were conducted. Specifically, double
mutagenesis at the 365th position and any of the 326th, 529th
and 472nd positions, and triple mutagenesis at the 365th, 472nd,
and 4 7 5th positions were examined.
Yamaoka 833 i-f 86; see also Final Action 10-21 and Ans. 5-14 (discussing
Yamaoka 833).
FF8. Yamaoka 833 disclosed Table 17, an excerpt of which is
reproduced below:
S365Y
(single
mnt.-1tion)
365Y + 326Q
365Y +472 .. {
T1\BLE 17
Double n.mtage.nesis U/ml. (culture medium)
5 mrvt 10mM
Glucose Maltose Mal/Gfo Glucose Malt\.mc Mal/Glc
1.42 0.02 2.46 0.05
***
2.28 0.01 0.6% " ""} ·'··'"-· o.cn 1.0%
***
0,98 0.051 .;; ")()/ -· ..... . d) L85 O.Cl42 2.31%1
Table 17 (in excerpt) shows that a double mutation of SEQ ID NO: 3, where
tyrosine is substituted at the 365 position and glutamine is substituted at the
326 position, decreased the specific activity maltose/glucose ratio to 0.6%
for 5mM and 1.0% for 1 OmM. Yamaoka 833 i-f 86; see also Final Action
10-21 and Ans. 5-14 (discussing Yamaoka 833). Table 17 also shows that a
double mutation of SEQ ID NO: 3, where tyrosine is substituted at both the
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3 65 and 4 72 positions, decreased the specific activity glucose/maltose ratio
to 5.2% and 2.3%, respectively at 5mM and lOmM. Yamaoka 833 i-f 86; see
also Final Action 10-21 and Ans. 5-14 (discussing Yamaoka 833).
FF9. In view of the results shown at Table 17, Yamaoka disclosed:
It was found that the substrate characteristics were
synergistically improved by the combinations with all the
positions examined, and it became clear that the substrate
characteristics could be further improved by a combination of a
mutation at the 365th position and amino acid substitution at
another position improving the substrate characteristics.
Yamaoka 833 i-f 87; see also Final Action 10-21 and Ans. 5-14 (discussing
Yamaoka 833).
FF 10. Yamaoka disclosed, the "combination effect of a mutation at
the 4 72 or 4 7 5th position, for which the substrate characteristic improving
effect was already confirmed by the inventors of the present invention, and a
mutation at a position other than the 365th position was examined."
Yamaoka 833 i-f 89; see also Final Action 10-21 and Ans. 5-14 (discussing
Yamaoka 833).
FFl 1. Yamaoka 833 disclosed, "[t]he synergistic effect was also
confinned for combinations of mutations at the 4 72 and 4 7 5th positions and
other positions," for example, the triple mutation 472Y + 475H + 326Q was
shown to decrease the maltose/ glucose specific activity reaction ratio to
4.3% and 6.1% for 5mM and lOmM, respectively. Yamaoka 833 i-fi-188-91;
see also Final Action 10-21 and Ans. 5-14 (discussing Yamaoka 833).
FF12. Yamaoka 833 disclosed, "it became clear that the mutations
including S365Y maintained about 90% of the specific activity for glucose,
and thus they were preferred mutations from the viewpoint of glucose
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measurement. Moreover, it also became clear that the S326Q mutation had
an effect of increasing the specific activity for glucose." Yamaoka 833
i-fi-192-93; see also Final Action 10-21 and Ans. 5-14, 29-30 (discussing
Yamaoka 833).
FF13. Yamaoka 833 disclosed, "it also became clear that use of the
mutation 326Q in addition to the mutation 365Y can increase the specific
activity for glucose, and relatively decrease the reactivity to maltose."
Yamaoka 833 i-f l 06; see also Final Action 10-21 and Ans. 5-14 (discussing
Yamaoka 833).
FF14. Sode disclosed SEQ ID NO: 3, which is 100% identical to SEQ
ID NO: 3 of the appealed claims. Final Action 14 (referencing App'x to
Office Action dated Mar. 9, 2012).
FF 15. Sode disclosed:
As a specific embodiment of the peptide enzyme of the present
invention, a protein having the amino acid sequence of SEQ ID
NO: 3 can be mentioned. Further, this peptide enzyme may be a
protein having the amino acid sequence containing substitution,
deletion, insertion or addition of one or more amino acid residues
in the amino acid sequence of SEQ ID NO: 3 so long as it has the
GDH activity ....
In the present invention, "one or more" means a number of 1 to
10, preferably 1 to 5, particularly preferably 1 to 3.
Sode col. 7, 1. 60 to col. 8, 1. 14, and claims 1-2; see also Final Action 14
and Ans. 5-6 (discussing Sode).
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DISCUSSION
The rejection of claims 1-3, 8-11, 15, 16, 18, and 19 under 35 US. C.
§ 102(b) as anticipated by Yamaoka 833.
Appellants contend Yamaoka 833 fails to disclose "each and every
element as set forth in the present claims." Br. 4. Appellants argue that,
although Yamaoka 833 discloses potential mutations of SEQ ID NO: 3 at
positions 365, 326, and 472, because it also discloses potential mutations at
several other positions and, at the positions of the appealed claims, discloses
several optional amino acid substitutions other than those recited by the
claims, "one of ordinary skill in the art would not at once envisage the
claimed mutations at positions 326, 365 and 472 with particular glutamine,
tyrosine and tyrosine, respectively." Id. 5.
We find that the claims are not anticipated by Yamaoka 83 3. Whether
or not the skilled artisan would "at once envisage" it, the specific
combination of SEQ ID NO: 3 mutations of the claims is not expressly or
inherently disclosed by Yamaoka 833. The reference does suggest such a
combination of mutations, but this is not enough for anticipation.
As stated in Arkley, an anticipatory reference under 35 U.S.C. § 102:
[M]ust clearly and unequivocally disclose the claimed compound
or direct those skilled in the art to the compound without any
need for picking, choosing, and combining various disclosures
not directly related to each other by the teachings of the cited
reference. Such picking and choosing may be entirely proper in
the making of a [§] 103, obviousness rejection, where the
applicant must be afforded an opportunity to rebut with objective
evidence any inference of obviousness which may arise from the
similarity of the subject matter which he claims to the prior art,
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Application 13/282,243
but it has no place in the making of a [ §] 102, anticipation
rejection.
In reArkley, 455 F.2d 586, 587-588 (CCPA 1972) (emphasis original).
Therefore, we reverse the anticipation rejection.
The rejection of claims 1-3, 8-11, 15, 16, 18, and 19 under 35 US. C.
§ 103(a) over Sode and Yamaoka 833.
Appellants have not presented persuasive evidence that the
Examiner's prima facie case that the claims would have been obvious is
incorrect.
Appellants renew the contention that the Examiner "fails to show a
teaching or suggestion of all of the claim elements." Br. 7. More
specifically, Appellants argue:
Yamaoka [833] fails to disclose the specific combination of the
mutations at positions 326, 365 and 472 with glutamine, tyrosine
and tyrosine, respectively, as set forth in the present claims [and]
Sode fails to cure the deficiency of Yamaoka [833] because Sode
does not even disclose any mutation of glucose dehydrogenase.
Id. 7. Appellants argue there would have been no motivation to replace the
amino acids (of SEQ ID NO: 3) at positions 326, 365, and 472 with
glutamine, tyrosine, and tyrosine, respectively." Id. 8. Appellants also
allege "unexpected superior properties of the claimed combination of
mutations, which are not present in the combinations of mutations in the
cited references;" the unexpected improvement being a decreased reactivity
to maltose relative to glucose (i.e., a decreased reaction ratio). Id. 9.
Appellants' arguments are unconvincing. Yamaoka 83 3 alone is
enough to have rendered the claimed subject matter obviousness, but
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Application 13/282,243
certainly so when combined with Sode, which also discloses SEQ ID NO: 3
and suggests mutating it for the very reason the invention does so, preferably
at 3 positions. See FF 1-FF 15. The amino acid replacements of the claims,
in view of the mutant GDH disclosed by Yamaoka 833 's finite suggested
possibilities, would have been obvious. Yamaoka 833 taught that each of
the mutations of SEQ ID NO: 3 at positions 326, 365, and 472, individually
or as a plurality of mutations, were advantageous in increasing the specific
activity of glucose with respect to maltose. FF4, FF6-FF13. Yamaoka 833
also taught the amino acids for replacement at each position, as claimed.
FF2, FF5, FF6, FF8, FFl 1, FF13. Yamaoka 833 also taught the synergistic
effect of combining such mutations to further improve the specific activity
of glucose and the desirability of testing the finite combinations of mutations
at the claimed positions to this end. FF 4, FF7-FF 13. Such disclosure
renders the claimed subject matter obvious. Where there is a need or market
pressure (as there would be here), picking one of a finite number of known
solutions to a known problem is obvious. KSR Int 'l Co. v. Teleflex Inc., 550
U.S. 398, 421 (2007).
Appellants contend that the data at Table 4 in the Specification is
evidence of unexpected results and the non-obviousness of the claims. We
are not persuaded. "[B]y definition, any superior property must be
unexpected to be considered evidence of non-obviousness. Thus, in order to
properly evaluate whether a superior property was unexpected, the [fact-
finder must] consider[] what properties were expected." Pfizer, Inc. v.
Apotex, Inc., 480 F.3d 1348, 1371 (Fed. Cir. 2007) (emphasis original;
internal citations omitted herein unless otherwise indicated). Here,
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Appellants present evidence of experimental results relating to some aspects
of the claimed invention (see generally, Br. 9-11); however, on the current
record (see, e.g., discussion supra), the evidence and results presented were
not "unexpected."
Besides the Examiner's determination that such results are not
commensurate with claim scope, i.e., they do not relate to a mutant having
only 80% identity to SEQ ID NO: 3, and additionally, that the results are not
"unexpected" in view of Yamaoka 833. Yamaoka 833, as discussed above,
urges combining mutations (and Sode suggests 3 mutations) to improve
glucose specificity respective of maltose in GDH and provides a roadmap of
such experimentation. Yamaoka 833 extolls the synergistic effect of such
combinations of mutations, identifies the positions to make amino acid
replacements, and identifies the claimed amino acids to be substituted.
Therefore, we are not persuaded by Appellants' arguments and affirm the
obviousness rejection.
The rejection of claims 1-3, 8-11, 15, 16, 18, and 19 under the
judicially created doctrine of obviousness-type double patenting as
unpatentable over claims 1, 3--8, 11, 13, 15, and 20-25 of Yamaoka 969 and
also over claims 1and4-10 of Yamaoka 529 in view of Yamaoka 833.
Appellants present overlapping arguments with respect to the two
double patenting rejections and, so, we address them together.
Appellants have not presented persuasive evidence that the
Examiner's prima facie case that the claims would have been obvious in
over the claims of Yamaoka 969 or the claims of Yamaoka 529 in view of
Yamaoka 833 is incorrect. Appellants' arguments are essentially repeated
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from those made with respect to the Yamaoka 833-Sode obviousness
rejection, discussed above.
Appellants argue the specific combination of mutations is not recited
in claims and that there would be no motivation to choose the claimed
mutations. Br. 14--16. The claims of Yamaoka 969 are essentially the same
as the disclosure of Yamaoka 833 and Yamaoka 833 is expressly invoked in
the rejection over the claims of the Yamaoka 529 claims. For the same
reasons set forth above with respect to the Yamaoka 833 reference, we are
unpersuaded by Appellants' arguments here and the respective rejection is
affirmed.
SUMMARY
The rejection of claim 1 under 35 U.S.C. § 102(b) as anticipated by
Yamaoka 833 is reversed. Claims 2, 3, 8-11, 15, 16, 18, and 19 fall with
claim 1. 3 7 C.F .R. § 41.3 7 ( c )(1 )(iv).
The rejection of claim 1 under 35 U.S.C. § 103(a) over Sode and
Yamaoka 833 is affirmed. Claims 2, 3, 8-11, 15, 16, 18, and 19 fall with
claim 1. 3 7 C.F .R. § 41.3 7 ( c )(1 )(iv).
The rejection of claim 1 under the judicially created doctrine of
obviousness-type double patenting as unpatentable over claims 1, 3-8, 11,
13, 15, and 20-25 of Yamaoka 969 is affirmed. Claims 2, 3, 8-11, 15, 16,
18, and 19 fall with claim 1. 37 C.F.R. § 41.37(c)(l)(iv).
The rejection of claim 1 under the judicially created doctrine of
obviousness-type double patenting as unpatentable over claims 1 and 4--10
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of Yamaoka 529 in view of Yamaoka 833 is affirmed. Claims 2, 3, 8-11,
15, 16, 18, and 19 fall with claim 1. 37 C.F.R. § 41.37(c)(l)(iv).
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
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