Ex Parte Shah et al

Board of Patent Appeals and Interferences

Mar 22, 2010

10035918 (B.P.A.I. Mar. 22, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
____________

Ex parte RAJIV SHAH and BAHAR REGHABI
____________

Appeal 2009-011224
Application 10/035,918
Technology Center 1600
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Decided: March 22, 2010
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Before LORA M. GREEN, RICHARD M. LEBOVITZ, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

LEBOVITZ, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on the appeal under 35 U.S.C. § 134 by the Patent
Applicant from the Patent Examiner’s rejections of claims 1, 3-8, 10-24, and
44-46. The Board’s jurisdiction for this appeal is under 35 U.S.C. § 6(b).
The rejection is affirmed.

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STATEMENT OF THE CASE
The claims are drawn to methods of screening for mutated glucose
oxidase (“GO”) enzymes which have peroxide resistant properties. Glucose
oxidases are utilized in biosensors to detect glucose (Spec. 3:1-14).
Hydrogen peroxide is produced as a by-product of the enzymatic reaction
(id. at 3:15-16). The peroxide molecule inactivates GO, limiting the
biosensor’s lifetime (id. at 3:20 to 4:2). To address this problem, a “directed
evolution” technique is described by the inventors which utilized genetic
engineering techniques to produce enzymes with improved peroxide-
resistant properties (id. at 5-6).
The claims 1, 3-8, 10-24, and 44-46 are pending. The claims stand
rejected by the Examiner as follows:
1. Claims 1, 3-5, 12-15, 18-24, 44, and 45 under 35 U.S.C. § 103(a)
as obvious in view of Valdes (In Vitro and In Vivo Degradation of Glucose
Oxidase Enzyme Used for an Implantable Glucose Biosensor, Diabetes
Technology & Therapeutics, Vol. 2, No. 3, pp. 367-376 (2000)), Cherry
(Directed evolution of a fungal peroxidase, Nature Biotechnology, Vol. 17,
pp. 379-384 (1999)), and Hatzinikolaou (A new glucose oxidase from
Aspergillus niger: characterization and regulation studies of enzyme and
gene, Applied Microbiology & Biotechnology, Vo. 46, pp. 371-381 (1996))
(Ans. 4);
2. Claim 16 and 17 under 35 U.S.C. § 103(a) as obvious in view of
Valdes, Cherry, Hatzinikolaou, and Misonix (Ultrasonic Liquid Processors,
Cole Parmer Catalog, p. 2112) (Ans. 7); and
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3. Claims 6-8, 10, 11, and 46 under 35 U.S.C. § 103(a) as obvious in
view of Valdes, Cherry, Hatzinikolaou, Wagner (EP 0 251 475 A1, Jan. 7,
1988), and Aldrich Catalog,1 p. 1005 (Ans. 8).
Claim 1 is representative and reads as follows:
1. A method for formulating an enzyme comprising:
obtaining a library of glucose oxidase genes;
creating a library of mutated glucose oxidase genes;
introducing each mutated glucose oxidase gene of the library into
separate expression vectors;
inserting the expression vectors into non-human host organisms;
growing colonies of the host organisms; and
screening the colonies for predefined, desired properties by
determining whether the colonies contain active glucose oxidase and
determining whether the colonies have predefined, desired peroxide resistant
properties,
wherein determining whether the colonies have predefined, desired
peroxide resistant properties comprises:
incubating the colonies in peroxide; and
determining whether the colonies have active glucose oxidase after
incubating the colonies in peroxide.

ISSUES ON APPEAL
The issues in this appeal are as follows:
Did the Examiner err in determining that it would have been obvious
to persons of ordinary skill in the art to apply Cherry’s genetic engineering
technique for selecting mutant peroxidase enzymes to glucose oxidase?
Does Valdes “teach away” from using Cherry’s genetic engineering
technique to solve the glucose oxidase stability problem because Valdes

1 As noted by Appellants, the Examiner did not include “Aldrich” in the
main statement of the rejection, but referred to it when describing the
grounds of the rejection (App. Br. 7).
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teaches a different direction and “entirely different” approach than utilized
by Cherry?
PRINCIPLES OF LAW
“Often, it will be necessary . . . to look to interrelated teachings of
multiple [references] . . . and the background knowledge possessed by a
person having ordinary skill in the art, all in order to determine whether
there was an apparent reason to combine the known elements in the fashion
claimed.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007). “[T]his
analysis should be made explicit,” and it “can be important to identify a
reason that would have prompted a person of ordinary skill in the relevant
field to combine the elements in the way the claimed new invention does.”
Id.
An obviousness “analysis need not seek out precise teachings directed
to the specific subject matter of the challenged claim, for a court can take
account of the inferences and creative steps that a person of ordinary skill in
the art would employ.” Id.
In assessing a claim’s obviousness, “a court must ask whether the
improvement is more than the predictable use of prior art elements according
to their established functions.” Id. at 417. “The combination of familiar
elements according to known methods is likely to be obvious when it does
no more than yield predictable results.” Id. at 416.
A reference may be said to teach away when a person of
ordinary skill, upon reading the reference, would be
discouraged from following the path set out in the reference, or
would be led in a direction divergent from the path that was
taken by the applicant. The degree of teaching away will of
course depend on the particular facts; in general, a reference
will teach away if it suggests that the line of development
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flowing from the reference’s disclosure is unlikely to be
productive of the result sought by the applicant.
In re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994).
“[A] reference may teach away from a use when that use would render
the result inoperable.” In re ICON Health and Fitness Inc., 496 F.3d 1374,
1381 (Fed. Cir. 2007).
FINDINGS OF FACT
Valdes
1. Valdes teaches that it has been proposed that glucose oxidase, commonly
used in glucose sensors, deactivates over time due to hydrogen peroxide, a
byproduct of the enzymatic reaction (Valdes, at 367-68 & 372-73).
2. Valdes teaches that GO deactivation can lead to failure of glucose sensors
and describes different approaches to protect the enzyme (id. at 367-68).
3. Valdes states that “[b]etter options [to protect GO], however, are to
simply prevent the degradation of the enzyme using other chemical agents,
or techniques.” (Id. at 375.)
4. As an example, Valdes describes immobilizing catalase with GO because
“catalase is the natural hydrogen peroxide destroying catalyst” (id.).
5. Valdes also describes avoiding hydrogen peroxide degradation by using
supports which deactivate the peroxide (id.).
6. Valdes concludes that “[f]urther research is therefore needed to make
GO[ ] less sensitive to H2O2 degradation” (id.).
Cherry
7. Cherry describes the use of enzymes as catalysts in commercial and
industrial applications: “As chemical catalysts are typically used under
conditions considerably different, and often harsher, than those found in the
environment, this will require enzymes that have been genetically altered to
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improve their performance under defined, application-specific conditions.”
(Cherry, 379, col. 1).
8. Cherry refers to a review which “cites a number of examples of the in
vitro evolution of enzymes from relatively ineffective catalysts to
commercially viable products by a variety of directed evolution techniques”
(id. at 379, col. 1; see also id. at 383, col. 2).
9. Cherry describes mutagenesis of a peroxidase enzyme to produce mutants
with greater temperature stability and resistance to oxidative damage by
hydrogen peroxide (id. at 382-83; at 383 (“Discussion”)).
Hatzinikolaou
10. Hatzinikolaou describes isolation and cloning of a new glucose oxidase
from Asperigillus niger (Hatzinikolaou, 371).

ANALYSIS
Claim 1 is drawn to a multi-step genetic engineering method
involving mutating a glucose oxidase gene and then screening for mutants
with “peroxide resistant properties.” The Examiner found that Cherry
described a genetic engineering method for producing enzymes resistant to
hydrogen peroxide having steps as recited in claim 1, with the difference that
Cherry performed the method on a peroxidase enzyme, not glucose oxidase
as claimed (Ans. 5-6). However, the Examiner found that Valdes had
identified peroxide deactivation as a problem associated with glucose sensor
failure (id. at 5). The Examiner determined that persons of ordinary skill in
the art would have had reason to apply Cherry’s technique to Valdes’
glucose oxidase enzyme to generate a mutant resistant to hydrogen peroxide,
solving the problem articulated in the Valdes publication (id. at 6-7).
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Appellants contend that the Examiner erred in this determination.
They argue that the prior art does not teach or suggest the claimed invention,
but rather teaches away from it. They contend that “[n]either Valdes et al.,
nor any prior art of record that relates to peroxide degredation [sic] of
glucose oxidase, describe or suggest the use of a gene mutation method for
addressing peroxide degredation [sic] of glucose oxidase.” (App. Br. 10).
In making an obviousness determination, the Examiner is not required
to identify explicit teachings in the prior art that would have led persons of
ordinary skill in the art to the claimed subject matter. KSR, 550 U.S. at 418.
Rather, as long as the Examiner provides a plausible reason as to why the
skilled worker would have been prompted to have made the claimed
invention, his burden is met. KSR, 550 U.S. at 418.
In this case, although Valdes made no mention of genetic engineering
techniques to solve the GO stability problem, the Examiner properly took
“account of the inferences and creative steps that a person of ordinary skill
in the art would employ,” and reasoned that the skilled worker would have
found it obvious to apply Cherry’s technique for producing peroxidase
resistance to the GO enzyme. Id. The Examiner’s determination is
supported by evidence because Cherry explicitly acknowledged the value of
its genetic engineering technique to improve enzyme performance in
commercial and industrial applications (FF 7-8). Persons of ordinary skill in
the art therefore would have reasonably extrapolated Cherry’s teaching to
solve the glucose oxidase problem posed by Valdes.
Appellants contend that Valdes refers to conventional methods, such
as using additives for deactivating hydrogen peroxide or other chemical
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methods (App. Br. 16), teaching away from using Cherry’s genetic
engineering technique. Appellants argue:
More specifically, Valdes et al. refer to completely
different directions taken by those most skilled in the art,
whereby the glucose oxidase enzyme is immobilized and
attached to a support that deactivates peroxide. “A reference
may be said to teach away when a person of ordinary skill,
upon reading the reference, . . . would be led in a direction
divergent from the path that was taken by the applicant.” Tec
Air, Inc. v. Denso Mfg. Mich. Inc., 192 F.3d 1353, 1360, 52
USPQ2d 1294, 1298 (Fed. Cir. 1999).
(App. Br. 21).
It is undisputed that Valdes proposes chemical, enzymatic, and
support techniques for protecting the GO enzyme. However, Valdes’ failure
to suggest genetic engineering techniques to solve the GO stability problem
is not a “teaching away” from the claimed method because merely proposing
an approach to a problem, would not have discouraged the skilled worker
from taking other approaches, particularly when such approaches had been
suggested by the prior art and shown to be successful in related systems.
Claims 6-8, 10, 11, 16, 17 and 46 are rejected over Valdes, Cherry,
and Hatzinikolaou as for claim 1, and further in view of other cited prior art.
Appellants challenge the rejections only to the extent that Valdes, Cherry,
and Hatzinikolaou do not each or suggested the claimed method. As we
have already found these arguments deficient for claim 1, we affirm the
additional rejections for the reasons cited by the Examiner.

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CONCLUSIONS OF LAW & SUMMARY
The Examiner did not err in determining that it would have been
obvious to persons of ordinary skill in the art to apply Cherry’s genetic
engineering technique to glucose oxidase in order to select for mutants with
peroxide resistant properties. Valdes did not “teach away” from using
Cherry’s genetic engineering technique to solve the glucose oxidase stability
problem identified by Valdes. The obviousness rejection of claim 1 is
affirmed. Claims 3-5, 12-15, 18-24, 44, and 45 fall with claim 1 because
separate reasons for their patentability were not presented. 37 C.F.R.
§ 41.37(c)(1)(vii).
As Appellants rely on the arguments made with respect to claim 1 as
to the remaining rejections, we also affirm the rejection of
claims 16 and 17 under 35 U.S.C. § 103(a) as obvious in view of
Valdes, Cherry, Hatzinikolaou, and Misonix; and
claims 6-8, 10, 11, and 46 under 35 U.S.C. § 103(a) as obvious in
view of Valdes, Cherry, Hatzinikolaou, Wagner, and Aldrich Catalog.

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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

alw

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