Ex Parte Wang et al

Patent Trial and Appeal Board

Dec 13, 2016

13856244 (P.T.A.B. Dec. 13, 2016)

United States Patent and Trademark Office
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
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Alexandria, Virginia 22313-1450
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APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
13/856,244 04/03/2013 Ping Wang TTC-87003/08wrg 4931
63796 7590 12/15/2016
DINSMORE & SHOHL LLP
P.O. BOX 7021
TROY, MI 48007-7021
EXAMINER
BOWERS, ERIN M
ART UNIT PAPER NUMBER
1653
NOTIFICATION DATE DELIVERY MODE
12/15/2016 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):
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte PING WANG, SONGTAO WU,
HONGFEI JIA, MASAHIKO ISHII, and MINJUAN ZHANG
Appeal 2014-009545
Application 13/856,244
Technology Center 1600
Before JEFFREY N. FREDMAN, TIMOTHY G. MAJORS, and
KRISTI L. R. SAWERT, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal1 under 35 U.S.C. § 134 involving claims to a process
for stabilizing a bioactive composition against inactivation by an organic
solvent. The Examiner rejected the claims as obvious. We have jurisdiction
under 35 U.S.C. § 6(b). We affirm.
1 Appellants identify the Real Parties in Interest as Toyota Motor
Engineering & Manufacturing North America, Inc., The University of
Minnesota, and the Toyota Motor Corporation (see App. Br. 1).
Appeal 2014-009545
Application 13/856,244
Statement of the Case
Background
“Bioactive macromolecules such as proteins, nucleic acids, and
functional enzymes may be utilized in various aspects of biomedical and
industrial applications” (Spec. 13). “Although proteins such as digestive
proteins or enzymes may be capable of decomposing and reacting with
various organic molecules, they are generally not thermally stable at
elevated temperatures. Additionally, such proteins or digestive enzymes are
generally not stable in a non-aqueous organic solvent” (Spec. 14).
The Claims
Claims 1—5 and 7—9 are on appeal. Independent claim 1 is
representative and reads as follows:
1. A process for stabilizing a bioactive composition against
inactivation by an organic solvent comprising:
forming hydrogel matrix pores around protein molecules;
reducing a water content within the hydrogel matrix pores
forming a hydrogel-protein composite, said step of reducing
comprising heating the hydrogel matrix to a temperature of from 20 to
80 degrees Celsius for a time period of 24 hours followed by air
drying at room temperature for one week;
and stabilizing activity of said protein molecules against
inactivation by an organic solvent by said step of forming and said
step of reducing.
The Issue
The Examiner rejected claims 1—5 and 7—9 under 35 U.S.C. § 103(a)
as obvious over Wang2 and Lee3 (Final Act. 3—8).
2 Wang et al., US 2008/0293117 Al, published Nov. 27, 2008 (“Wang”).
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Application 13/856,244
The Examiner finds “Wang teaches the encapsulation of chymotrypsin
and glucose oxidase in acrylamide hydrogels”; that the “hydrogel entrapped
enzymes were exposed to a thermal pretreatment in an oven”; and the
“thermal pretreatment conditions for the hydrogel-entrapped glucose oxidase
were 20-80 °C for 24 hours” (Final Act 3 4).
The Examiner acknowledges that “Wang does not teach that the
hydrogel matrix was air dried at room temperature for one week” (Final Act.
6).
The Examiner finds “Lee teaches the immobilization of lysozyme in
Pluronic hydrogels .... The polymerized gel disks were dried in air for one
day and then dried in an oven for one day” (id. ).
The Examiner finds it obvious “to air dry the hydrogels in addition to
drying them in the oven because Lee teaches that air drying in addition to
oven drying is a known method of drying hydrogels” (id.). The Examiner
finds it obvious “to determine all operable and optimal drying times for the
hydrogel-protein composites because the drying time is an art-recognized
result-effective variable known to affect the residual water content, which
would have been optimized in the art to provide maximum protein stability”
(Final Act. 7).
The issue with respect to this rejection is: Does the evidence of
record support the Examiner’s conclusion that Wang and Lee render obvious
3 Lee et al., Photo-crosslinkable, thermo-sensitive and biodegradable
Pluronic hydrogels for sustained release ofprotein, 15 J. Biomater. Sci.
Polymer Edn 1571-1583 (2004) (“Lee”).
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Application 13/856,244
a process of stabilizing a hydrogel encapsulated enzyme by “air drying at
room temperature for one week” after oven drying as required by claim 1?
Findings of Fact
1. Wang teaches “a need in the art for a thermally stable bioactive
composition and process for producing the bioactive composition that may
be stable for various environmental stresses including elevated temperature
and acidity” (Wang 17).
2. Wang teaches, in Example 1, forming hydrogel matrix pores
around protein molecules by “[entrapment of Glucose Oxidase (GOx) into
Polyacrylamide Hydrogel” (Wang H 46-47; see Final Act. 3 4).
3. Wang teaches “[ijncubation in an oven under specific
temperatures—For hydrogel-entrapped glucose oxidase, an effective
pretreatment temperature is illustratively in the range from 20 degree Celsius
to 80 degree Celsius” (Wang 1 63).
4. Wang teaches the “estimated half-life of the thermal pretreated
glucose oxidase molecules is greater than 500 days compared to minutes for
the freely unbound native counterparts” (Wang 1 65).
5. Wang teaches “the stability of the biological macromolecules
may be improved through the porosity control of the resultant hydrogel
through the manipulation of the water content of the hydrogel such as
removing the free water located within the hydrogel” (Wang 137).
6. Wang teaches
a thermal pretreatment may include a heat-assisted procedure to
remove water from the hydrogel. Various factors including the
degree of temperature, the period of time for heat treatment, the
starting water content of the hydrogel, as well as the molecular
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weight of the targeted bioactive macromolecules will have a
result on the stability of a hydrogel matrix.
(Wang 139).
7. Wang teaches “[f]or example, a hydrogel specimen having a
glucose oxidase may be pretreated at temperatures of from 20 to 110 degrees
Celsius for time periods of from 24 hours to 7 days in length” (Wang 141)
8. Wang teaches that “heat treatment to form a hydrogel protein
structure providing increased stability for the protein macromolecule ....
Various external stresses including acidic, basic, inorganic salts or organic
solvents and heat may cause the denaturization of the proteins” (Wang 136).
9. Wang teaches, in Example 9: “Stability of Thermal Pretreated
Hydrogel-Entrapped Glucose Oxidase (GOx) Under a Combined Harsh
Condition” where “[stability was investigated under a combined harsh
condition including a combination of high temperature and polar solvent”
and “the combined harsh condition of dry heat of 75 degrees Celsius and the
presence of ethanol elicits no significant effect on the thermal preheated
GOx over an examined period of 1200 hours compared to the native GOx
counterpart that gets denatured and inactivated instantaneously within a
matter of minutes” (Wang H 67—69).
10. Lee teaches “[m]any kinds of natural and synthetic polymeric
hydrogels have been widely used for sustained delivery of bioactive
macromolecules” (Lee 1571).
11. Lee teaches “lysozyme was dissolved in the Pluronic macromer
solution . . . [ajfter UV induced polymerization, gel-disks with a diameter of
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Application 13/856,244
1 cm were excised . . . [t]he above gel-disks were dried in air for 1 day, and
then in a vacuum oven for 1 day” (Lee 1574).
Principles of Law
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
KSR Inti Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). “If a person of
ordinary skill can implement a predictable variation, § 103 likely bars its
patentability.” Mat417.
Analysis
We adopt the Examiner’s findings of fact and reasoning regarding the
scope and content of the prior art (Final Act. 3—8; FF 1—11). We address
Appellants’ arguments below.
Appellants contend that “[i]t is clear that neither reference teaches
room temperature air drying for one week as is required by all presently
pending claims” (App. Br. 2). Appellants also contend “there is no
suggestion in Wang et al., Fee et al., or any other cited reference or evidence
of record to modify the Wang et al. drying step to add additional drying time
for any purpose, including for providing solvent stability” (App. Br. 3).
Appellants contend “drying was not recognized as a variable that would lead
to organic solvent stability” and that a “one week air drying step was not
recognized as an adjustable variable that would or could impart solvent
stability to a hydrogel entrapped enzyme” (App. Br. 5).
We do not find these arguments persuasive not just because the
rejection is for obviousness but because Wang teaches “a hydrogel specimen
having a glucose oxidase may be pretreated at temperatures of from 20 to
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110 degrees Celsius for time periods of from 24 hours to 7 days in length”
(FF 7) to improve stability (FF 5). Thus, Wang’s pretreatment range
expressly encompasses drying at room temperatures of about 20 to 25 °C
and time periods of a week (seven days) (FF 7). We also agree with the
Examiner that “the instantly claimed drying time would be within the realm
of routine experimentation” (Final Act. 7).
Indeed, Wang expressly recognizes that the stability of hydrogel
entrapped enzymes may be optimized by removing water from the hydrogel
(FF 5), that thermal pretreatment removes water (FF 6) and improves
stability relative to organic solvents (FF 9), and that factors involved in the
optimization of water removal by heat treatment include “the degree of
temperature” and “the period of time for heat treatment” (FF 6). “[WJhere
the general conditions of a claim are disclosed in the prior art, it is not
inventive to discover the optimum or workable ranges by routine
experimentation.” In re Alter, 220 F.2d 454, 456 (CCPA 1955). This rule is
appropriate in cases such as this one where the optimized variables of
temperature and time for removal of water from enzyme containing
hydrogels were identified by the art as “result-effective variable[s].” In re
Applied Materials, Inc., 692 F.3d 1289, 1295 (Fed. Cir. 2012) (citing In re
Antonie, 559 F.2d 618, 620 (CCPA 1977)).
In addition, Wang recognizes that stability is not solely related to
elevated temperature but may also be related to chemical conditions such as
acidity (FF 1), and Wang specifically identifies stressors including organic
solvents that may be addressed by increased stability (FF 8). Example 9 of
Wang demonstrates improved stability of heat pretreated hydrogel
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encapsulated enzymes when exposed to an organic solvent relative to
untreated enzymes (FF 9).
Appellants contend that “one of skill in the art would be dissuaded
from adding an air drying step from the teaching of Wang et al. as paragraph
[0063] clearly teaches that all water is removed by 24 hours” (App. Br. 3).
We do not find this argument persuasive because there is no statement
in paragraph 63 of Wang that all water is removed by 24 hours (see Wang
1 63; cf Ans. 13). Moreover, a teaching away requires a reference to
actually criticize, discredit, or otherwise discourage the claimed solution.
See In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004) (“The prior art’s
mere disclosure of more than one alternative does not constitute a teaching
away from any of these alternatives because such disclosure does not
criticize, discredit, or otherwise discourage the solution claimed”). Here,
Wang teaches towards the invention by suggesting treatment may extend to
“7 days in length” (FF 7).
Appellants contend that “[njowhere does Lee et al. suggest
lengthening the air drying step to one week, that a one week air drying step
will improve enzyme stability at all, or that organic solvent stability can be
achieved” (App. Br. 4). Appellants contend that “one looking to trap an
enzyme in a hydrogel matrix to stabilize its solvent exposed activity would
not look to Lee et al. for any teaching” (App. Br. 4)
We do not find this argument persuasive because Lee is relied upon
by the Examiner to demonstrate a drying process for hydrogel encapsulated
enzymes that utilizes both oven drying and air drying (FF 11), not for
specifically teaching the period of time for air drying. Moreover, it is Wang
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that teaches drying increases half-life of hydrogel encapsulated enzymes (FF
4—5). “Non-obviousness cannot be established by attacking references
individually where the rejection is based upon the teachings of a
combination of references.” In re Merck & Co., 800 F.2d 1091, 1097 (Fed.
Cir. 1986). A reference “must be read, not in isolation, but for what it fairly
teaches in combination with the prior art as a whole.” Id.
Appellants contend that “[n]o variable is taught as affecting the
stabilization of an enzyme against inactivation by an organic solvent as is
the crux of all pending claims” (App. Br. 6).
We are not persuaded. We recognize that the Examiner’s reason for
optimizing stability of pretreating hydrogel encapsulated enzymes “at
temperatures of from 20 to 110 degrees Celsius for time periods of from 24
hours to 7 days in length” (FF 7) may not be identical to Appellants’ reasons
for performing the same steps, though Wang specifically identifies stressors
including organic solvents that may be addressed by heat treatment for
increased stability (FF 8—9). However, that the prior art has a different
reason or motivation is of no moment as long as there is a sufficient reason
to perform the same water removing process on the same hydrogel
encapsulated enzyme material for the same period of time. See In re Kemps,
97 F.3d 1427, 1430 (Fed. Cir. 1996) (“[T]he motivation in the prior art to
combine the references does not have to be identical to that of the applicant
to establish obviousness.”).
Appellants contend the “addition of such a drying time is not taught or
suggested by any cited reference, and the claimed lengthy drying time is not
a variable expected to provide solvent stability to a hydrogel entrapped
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enzyme. It is submitted that Examiner’s conclusion is nothing more than
improper hindsight bias” (App. Br. 6).
We are not persuaded. While we are fully aware that hindsight bias
may plague determinations of obviousness, Graham v. John Deere Co., 383
U.S. 1, 36 (1966), we are also mindful that the Supreme Court has clearly
stated that the “combination of familiar elements according to known
methods is likely to be obvious when it does no more than yield predictable
results.” KSR, 550 U.S. at 416. In the instant case, removing water from
hydrogels with encapsulated enzymes by both air drying and oven drying as
taught by Lee (FF 11) by selecting times and temperatures expressly within
the ranges taught by Wang (FF 5—7) against stressors including organic
solvents (FF 8—9), supports the Examiner’s position because a “prima facie
case of obviousness typically exists when the ranges . . . overlap the ranges
disclosed in the prior art.” In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir.
2003). Appellants provide no evidence of any secondary consideration or
unexpected results to weigh with the prima facie case of obviousness.
Conclusions of Law
The evidence of record supports the Examiner’s conclusion that the
Wang and Lee references render obvious a process of stabilizing a hydrogel
encapsulated enzyme by “air drying at room temperature for one week” after
oven drying as required by claim 1.
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SUMMARY
In summary, we affirm the rejection of claim 1 under 35 U.S.C.
§ 103(a) as obvious over Wang and Lee. Claims 2—5 and 7—9 fall with claim
1.
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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