Ex Parte King et al

Patent Trial and Appeal Board

Dec 13, 2012

12180262 (P.T.A.B. Dec. 13, 2012)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte RICHARD S. KING and GEORGE LAWRENCE GROBE III
__________

Appeal 2011-011241
Application 12/180,262
Technology Center 1600
__________

Before LORA M. GREEN, MELANIE L. McCOLLUM, and
STEPHEN WALSH, Administrative Patent Judges.

GREEN, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. § 134 from the
Examiner‟s rejection of claims 31, 34-41, 43, and 46-58. We have
jurisdiction under 35 U.S.C. § 6(b).
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STATEMENT OF THE CASE
Claims 31 and 41 are representative of the claims on appeal, and read
as follows:
31. A method for producing a hydrogel composition comprising water
and a crosslinked hydrophilic polymer, wherein the hydrogel composition
has (a) an ultimate tensile strength of about 10 kPa or more, (b) a
compressive strength of about 70 kPa or more, or (c) an ultimate tensile
strength of about 10 kPa or more and a compressive strength of about 70 kPa
or more, the method comprising the steps of:
(a) providing a compression mold having an internal volume,
(b) providing a hydrogel precursor in powder or pellet form
comprising a melt-processable, radiation crosslinkable, hydrophilic polymer
which is poly(ethyleneoxide) having an average molecular weight of about
1,000,000 atomic mass units or greater,
(c) filling at least a portion of the internal volume of the compression
mold with the precursor,
(d) compressing the precursor contained within the compression mold
to form a molded body therefrom,
(e) irradiating at least a portion of the molded body by exposing the
molded body to gamma, X-ray, or electron beam radiation the absence of
water, to crosslink at least a portion of the hydrophilic polymer contained
within the molded body, and
(f) hydrating the irradiated molded body to form a hydrogel
composition therefrom;
wherein the hydrogel composition has a water content of at least 75%
by weight.

41. A method for producing a hydrogel composition comprising water
and a crosslinked hydrophilic polymer, wherein the hydrogel composition
has (a) an ultimate tensile strength of about 10 kPa or more, (b) a
compressive strength of about 70 kPa or more, or (c) an ultimate tensile
strength of about 10 kPa or more and a compressive strength of about 70 kPa
or more, the method comprising the steps of:
(a) providing a dispersion comprising a peroxide crosslinking agent,
(b) providing a hydrogel precursor in powder or pellet form
comprising a melt processable, hydrophilic polymer which is
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poly(ethyleneoxide) having an average molecular weight of about 1,000,000
atomic mass units or greater,
(c) coating at least a portion of the hydrogel precursor with the
dispersion,
(d) providing a compression mold having an internal volume,
(e) filling at least a portion of the internal volume of the compression
mold with the coated precursor produced in step (c),
(f) compressing the precursor contained within the compression mold
to form a molded body therefrom and crosslink in the absence of water at
least a portion of the hydrophilic polymer contained within the molded body,
and
(g) hydrating the molded body to form a hydrogel composition
therefrom;
wherein the hydrogel composition has a water content of at least 75%
by weight.

The following grounds of rejection are before us for review:
I. Claims 31, 34-40, 52, 53, and 56-58 stand rejected under 35 U.S.C.
§ 103(a) as being rendered obvious by the combination of
Doytcheva
1
and Zainuddin
2
(Ans. 4).
II. Claims 41, 43, 46-51, 54 and 55 stand rejected under 35 U.S.C.
§ 103(a) as being rendered obvious by the combination of
Doytcheva and Froix
3
(Ans. 14).

We affirm-in-part.

1
Doytcheva et al., Ultraviolet-Induced crosslinking of Solid Poly(ethylene
Oxide), 64 J. APPLIED POLYMER SCIENCE 2299-2307 (1996).
2
Zainuddin et al., Radiation-induced degradation and crosslinking of
poly(ethylene oxide) in solid state, 253 J. RADIOANALYTICAL AND NUCLEAR
CHEMISTRY, 339-344 (2002).
3
Froix, US 4,871,785, issued Oct. 3, 1989.
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ANALYSIS (Rejection I)
The Examiner rejects claims 31, 34-40, 52, 53, and 56-58 as being
rendered obvious by Doytcheva and Zainuddin (Ans. 4).
The Examiner finds that Doytcheva teaches all of the steps of the
method of claim 31 except for “irradiating at least a portion of the molded
body by exposing the molded body to gamma, X-ray, or electron beam
radiation the absence of water, to crosslink at least a portion of the
hydrophilic polymer contained within the molded body” (Ans. 4-5). The
Examiner finds that “Zainuddin teaches γ-irradiation of solid poly(ethylene
oxide)” (id. at 5). Specifically, the Examiner finds that Zainuddin teaches
that a γ-irradiation dose of 20 kGy (2 Mrad) induces crosslinking in
powdered poly(ethylene oxide).
The Examiner concludes that it would have been obvious to the
ordinary artisan “to utilize 2 Mrad of γ-radiation to assist in the crosslinking
of the composition of Doytcheva … [s]ince the radiation of both Doytcheva
and Zainuddin are exposed to poly(ethylene oxide) in dry solid state for the
same purpose (crosslinking), their utilization together would necessarily
result in effective crosslinking of poly(ethylene oxide)” (id. at 5-6).
As to claim 31, Appellants argue that Doytcheva does not teach
“gamma, X-ray, or electron beam radiation in the absence of water,” but
instead uses UV radiation (App. Br. 7). According to Appellants, the
“process requirements are completely different and the types of samples that
can be so treated are also completely different” (id. at 8). As to the different
process requirements, Appellants provide the example that UV
photoinitiation of a cross-linking reaction requires a photoinitiator, while
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gamma-irradiation does not (id.). Appellants assert that when Doytcheva
does mention gamma irradiation, it is in the context of dilute aqueous
solutions of polyethylene oxide (PEO) (id. at 8-9).
Appellants further assert that the Examiner has misconstrued
Zainuddin (id. at 9). Appellants assert that Table 1 of Zainuddin has nothing
to do with cross-linking of PEO, but “instead speaks to the decrease in
molecular weight observed when powdered PEO (mw = 630,000) is
subjected to irradiation” (id.). Appellants argue that “[e]xcept for the one
data point (2 kGy of irradiation in a vacuum), the data shows irradiation
causes an overall degradation of the polymer” (id.). As to the 20 kGy point,
Appellants assert that Zainuddin explains that is “an effect of the broadening
molecular weight distribution and not an actual overall increase in molecular
weight” (id. at 9-10 (citing Zainuddin, p. 342, col. 2, first paragraph)).
Appellants further assert that the combination of the Examiner also ignores
Doytcheva‟s teaching that too much irradiation is detrimental to the
formation of the hydrogel (id. at 11 (citing Doytcheva, p. 2305, col. 2, ¶2)).
Appellants also argue that Zainuddin teaches measuring the molecular
weight of the irradiated PEO by HPLC/GPC, which is a technique used to
determine the molecular weight of polymers dissolved in solution (id. at 9).
According to Appellants, “[a] hydrogel will not flow through a HPLC/GPC;
rather it is a semi-solid material that can be held and touched” (id.)(emphasis
added). Appellants thus assert that Zainuddin‟s use of liquid
chromatography demonstrates that “Zainuddin‟s PEO is not a hydrogel”
(id.).
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Appellants assert further that Doytcheva and Zainuddin teach away
from the combination (id. at 10). Appellants reiterate that Doytcheva only
teaches the use of gamma-irradiation to form PEO hydrogels in dilute
aqueous solutions, and dismiss that technique in favor of use of UV radiation
(id.). Appellants further assert that the “overall teaching of Zainuddin is that
the γ-irradiation causes the PEO to decrease in molecular weight” (id. at 10).
We have carefully considered Appellants‟ arguments, but do not find
them convincing. Doytcheva teaches the use UV radiation in the presence of
a photoinitiator, such as benzophenone, to cross-link dried poly(ethylene
oxide) (PEO) (Doytcheva, Abstract; see also id. at p. 2300, first column,
“Sample Preparation”). Doytcheva teaches that the cross-linked polymers
have a number of applications, such as wound dressings and controlled-
release drug systems (id. at 2299, first col.). Doytcheva notes that cross-
linked PEO may be obtained using γ-irradiation of degassed dilute aqueous
solution, and also teaches that the “ease, relative safety, and low cost of UV-
induced crosslinking should provide significant advantages for many
applications over other methods” (id. at 2299). Doytcheva does not teach
the use of γ-irradiation to polymerize the dried PEO.
Zainuddin teaches that PEO is widely used in the form of cross-linked
hydrogels, for wound healing and drug delivery (Zainuddin, p. 339, first
column). Zainuddin studied the effects of γ-irradiation on solid PEO (id.,
Abstract). Zainuddin teaches that at doses over 15kGy, the ratio between the
two competing processes of chain scission and intermolecular cross-linking
changes in favor of intermolecular crosslinking (id. at 342, first column).
Zainuddin also teaches that “[s]cission dominates for doses up to ca. 15 kGy,
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while for higher doses intermolecular crosslinking gains in importance”
(Zainuddin, Abstract).
Zainuddin teaches
In order to gain more information on the scission and
crosslinking reactions in our system, the samples were also
analyzed by viscometry and the changes in the molecular
weight distribution were followed by HPLC/GPC. As can be
seen from Fig. 4, irradiation within the applied dose range does
not induce large changes in viscosity of PEO solutions. The
viscosity undergoes some decrease in the first phase of
irradiation, but at higher doses some increase is observed, in
agreement with the data on molecular weight. The complexity
of these processes is well illustrated by the changes in
molecular weight distribution (Fig. 1). The two polymer
fractions present in the initial sample seem to behave in a
different way upon irradiation. The maximum of the broad
peak of lower molecular weight becomes shifted towards lower
values, indicating the occurrence of scission reactions, while the
intensity of the high-molecular-weight peak increases, and a
shoulder is built in the very high molecular weight region,
giving evidence of effective intermolecular crosslinking. As a
result of that, the distribution of molecular weight becomes
broader, the Mw/Mn parameter changing from 2.9 to over 4
(Table 1). There may be at least two reasons for the observed
behavior. It might be possible that the yields of intermolecular
crosslinking in solid-state samples depend on the molecular
weight, so that in the case of initial bimodal distribution both
fractions may have different ratios of G(s) to G(x). Another
explanation may be that the kinetics and yields of scission and
crosslinking are different in the crystalline and amorphous
phase. At present, it is difficult to differentiate between these
two effects.

(Id. at p. 342, second column.)
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Thus, as taught by Zainuddin, while at γ-irradiation doses over 15
kGy, chain scission may still occur, the competing reactions shift from such
scission to intermolecular cross-linking, and that effective intermolecular
crosslinking is occurring. Thus, Zainuddin demonstrates that at doses of γ-
irradiation over 15 kGy, intermolecular crosslinking of dry PEO does occur,
and is favored over scission. We therefore agree with the Examiner that it
would have been obvious to the ordinary artisan to use γ-irradiation doses
over 15 kGy as taught by Zainuddin to crosslink the dried PEO in the
process taught by Doytcheva with a reasonable expectation of success of
arriving at the claimed process. See In re O’Farrell, 853 F.2d 894, 903
(Fed. Cir. 1988) (noting that all that is required is a reasonable expectation
of success, not absolute predictability of success). Stated differently, the
ordinary artisan would understand that the crosslinking process taught by
Doytcheva that uses UV radiation and a photoinitiator could be performed
with the crosslinking process taught by Zainuddin that only requires the use
of γ-irradiation doses over 15 kGy. In that regard, we note that claim 31
does not exclude the possibility that scission may also be occurring along
with the cross-linking.
The motivation for combining the references comes from the
references themselves, as both references are drawn to crosslinking of dry
PEO. The Supreme Court has emphasized that “the [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.” KSR
Int’l v. Teleflex Inc., 550 U.S. 398, 418 (2007). “If a person of ordinary skill
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can implement a predictable variation, § 103 likely bars its patentability.
(Id. at 417.)
While Appellants argue that by virtue of Zainuddin‟s use of
HPLC/GPC to determine the molecular weight of the polymer the polymer
formed cannot be a hydrogel (see Zainuddin, p. 340, second column),
Appellants provide no evidence to support that assertion, and as noted by the
Court of Appeals for the Federal Circuit, attorney argument cannot take the
place of evidence lacking in the record. Estee Lauder Inc. v. L’Oreal, S.A.,
129 F.3d 588, 595 (Fed. Cir. 1997).
We further conclude that neither Doytcheva nor Zainuddin teach away
from the combination.
Under the proper legal standard, a reference will teach away
when it suggests that the developments flowing from its
disclosures are unlikely to produce the objective of applicant‟s
invention. A statement that a particular combination is not a
preferred embodiment does not teach away absent clear
discouragement of that combination.

Syntex (U.S.A.) LLC v. Apotex, Inc., 407 F.3d 1371, 1380 (Fed. Cir. 2005)
(citations deleted).
Here, the mere fact that Doytcheva teaches that the use of UV
crosslinking with a photoinitiator has benefits over the use of γ-irradiation
on dilute aqueous solution of PEO is not a teaching away from the use of γ-
irradiation in general to crosslinking PEO. We have also considered
Doytcheva‟s teaching as page 2305, column 2, paragraph 2, which
Appellants assert teaches that too much irradiation is detrimental to the
formation of the hydrogel.
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What Doytcheva in fact teaches is:
The influence of the irradiation duration on crosslinking
efficiency is shown in Figure 4. It can be seen that irradiation
times above 20 min are sufficient to achieve more than 90% gel
fraction yield. Maximal crosslink density is observed in the
interval of 30-60 min irradiation. At an irradiation time of 80
min, an increase in equilibrium swelling and decrease in
crosslinking density is observed at constant GF yield. This is
most likely due to the competitive process of polymer chain
scission at extended irradiation times. The optimal irradiation
duration in the employed experimental conditions is thus
between 30 and 40 min.

(Id.)
The above teaching of Doytcheva relates to UV radiation, and not γ-
irradiation. Moreover, it demonstrates that it was within the level of skill of
the ordinary artisan to monitor the crosslinking reaction to obtain optimal
crosslinking efficiency.
Appellants assert that the Examiner‟s finding that the process taught
by the combination of Doytcheva and Zainuddin would inherently produce a
hydrogel having the claimed properties, i.e., tensile strength and
compressive strength, is incorrect, as the combination does not teach the
claimed process (App. Br. 11). Appellants assert that “the examiner has
„created‟ a process that is wholly distinct from the claimed process or the
process in either Doytcheva or Zainuddin” (id.). That argument is not found
to be convincing for the reasons set forth above.
We thus affirm the rejection of claim 1 as being rendered obvious by
the combination of Doytcheva and Zainuddin. Claims 35-37, 40, and 58 fall
with claim 31 (App. Br. 12, 15, and 21).
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Claim 34 is drawn to the method of claim 31, “wherein the precursor
is compressed at a pressure of about 3,800 kPa to about 14,000 kPa during
step (d).” The Examiner finds that 150 kG/cm
2
is about 14,000 kPa (Ans.
5).
Appellants note that 150 kG/cm
2
is equal to 14,710 kPA, which
Appellants assert is not about 14,000 kPa (App. Br. 12). Appellants assert
that 14,710 kPA does not “abut the claimed range, but is substantially
greater than the claimed range” (id.).
During prosecution before the Office, claims are to be given their
broadest reasonable interpretation consistent with the Specification as it
would be interpreted by one of ordinary skill in the art. In re American
Academy Of Science Tech Center, 367 F.3d 1359, 1364 (Fed. Cir. 2004).
“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.” In re Zletz, 893 F.2d 319, 322 (Fed. Cir. 1989). Moreover, it is
during prosecution that applicants have “the opportunity to amend the claims
to obtain more precise claim coverage.” American Academy, 367 F.3d at
1364.
Here, Appellants do not point to any evidence that the ordinary artisan
would not interpret a range of “about 3,800 kPa to about 14,000 kPa” as not
encompassing 14,710 kPA. We thus affirm the rejection as to claim 34.
Claim 38 is drawn to the method of claim 31, “wherein the molded
body is hydrated by submerging at least a portion of the molded body in an
aqueous solution having a temperature of about 50°C to about 90 °C for
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about 120 hours to about 220 hours.” The Examiner finds that as Doytcheva
teaches heating the PEO up to 120°C for being pressed in the mold, and that
the composition is tested for swelling at room temperature (Ans. 12). Thus,
according to the Examiner, “one of ordinary skill in the art would conclude
that the swelling occurred at a minimum of about 25°C or higher since the
step which can immediately precede the swelling step can be at elevated
temperatures with no indication of a cooling step” (id. at 13).
Appellants argue that “neither the claimed temperature nor time is
disclosed or suggested by Doytcheva or Zainuddin” (App. Br. 13).
Appellants further assert that Doytcheva determines the equilibrium degree
of swelling a room temperature, which is distinct from the “about 50°C to
about 90°C” required by the claim (id. at 13-14).
We agree with Appellants that the Examiner has not established a
prima facie case of obviousness as to claim 38. Doytcheva in fact teaches
that the PEO samples were allowed to cool under pressure to ambient
temperature, and also specifically teaches that the equilibrium degree of
swelling was determined at room temperature (Doytcheva, p. 2300, first and
second columns, “Preparation of PEO Samples by Press-molding” and
“Swelling”). We thus reverse the rejection as to claim 38. As claim 39
depends on claim 38, we reverse the rejection as to that claim as well.
Claims 52 and 53 require the use of a second polymer, either by
including a second polymer in the hydrogel precursor (claim 52) or by
incorporating a second polymer into the hydrogel (claim 53). The Examiner
concludes that one would have been motivated to include a second polymer
“to allow for modification of tensile strength, consistency, and amount of
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crosslinking” (Ans. 7). Appellants argue that Doytcheva does not teach or
suggest the inclusion of a second polymer, much less address or describe
how adding a second polymer would modify the tensile strength (App. Br.
16-17).
We agree with Appellants that the Examiner has failed to set forth a
prima facie case of obviousness as to claims 52 and 53. “[R]ejections on
obviousness grounds cannot be sustained by mere conclusory statements;
instead, there must be some articulated reasoning with some rational
underpinning to support the legal conclusion of obviousness.” In re Kahn,
441 F.3d 977, 988 (Fed. Cir. 2006), cited with approval in KSR Int’l Co. v.
Teleflex Inc., 550 U.S. at 417-18. The Examiner‟s rejection is too
conclusory to pass the Kahn test.
Independent claims 56 and 57 are drawn to a drug delivery device and
a wound dressing comprising a hydrogel composition, respectively. The
Examiner finds that Doytcheva teaches that the PEO hydrogels are known to
be drug delivery devices and wound dressings, and that a controlled-release
drug system must necessarily have a drug present (Ans. 13). With respect to
that rejection, Appellants essentially reiterate the arguments made with
respect to claim 31 (App. Br. 17-21; see also Reply Br. 8). We thus affirm
the rejection as to claims 56 and 57 for the reasons set forth with respect to
claim 31.

ANALYSIS (Rejection II)
The Examiner rejects claims 41, 43, 46-51, 54, and 55 as being
rendered obvious by the combination of Doytcheva and Froix (Ans. 14).
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The Examiner relies on Doytcheva as set forth above (see id. at 14-
15). The Examiner notes that Doytcheva “fails to directly teach that benzoyl
peroxide is present in the composition” (id.).
The Examiner finds that “Froix teaches that benzoyl peroxide is
known to aid in the crosslinking of polyethylene oxide (see entire document,
for instance, last paragraph of column 7 and first paragraph of column 8)”
(id.). Thus, the Examiner concludes it would have been obvious to include
benzoyl peroxide to ensure crosslinking.
Appellants argue that the Examiner has misconstrued Froix (App. Br.
21). Appellants assert that the ordinary artisan “would understand
„polymerization‟ to refer to the polymerization of the methacrylate groups,”
and that the “PEO that will be included in the network is simply trapped in
the crosslinked network as uncrosslinked molecules” (id. at 22).
We agree with Appellants that the Examiner has not established it
would have been prima facie obvious to combine Doytcheva with Froix to
arrive at the claimed invention.
Froix is drawn to a contact lens composition which “may employ
conventional polymer materials, such as HEMA and polyvinyl pyrrolidone”
(Froix, col. 2, ll. 19-27). Froix teaches further that “the contact lenses and
compositions of the invention contain significant amounts of the
polyethylene oxide (PEO) unit -(CH2CH2O)n- either as part of the copolymer
forming the backbone, as side chains to said backbone, as a blend with the
polymeric materials, or as a cross linker” (id. at col. 2, ll. 34-40).
Froix also teaches “the compositions are prepared using conventional
polymerization techniques, including UV and peroxide catalyzed
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polymerizations” (id. at col. 7, ll. 52-54). Froix, teaches however, that “PEO
polymers wherein n is 5-300 may be added to the mixture to be polymerized,
presumably forming blends which hold the PEO in place non-covalently, or
in which the PEO is esterified to one of the polymer-forming units and
winds up as a side chain” (id. at col. 8, ll. 44-49).
Therefore, contrary to the finding of the Examiner, Froix does not
teach that benzoyl peroxide is known to aid in the crosslinking of
polyethylene oxide. And in fact, Froix teaches that when the mixture is
polymerized, the PEO is held in place non-covalently. Thus, the ordinary
artisan would not have looked to Froix for a method of crosslinking PEO as
suggested by the Examiner. We therefore reverse the rejection.

SUMMARY
We affirm the rejection of claims 31, 34-40, 52, 53, and 56-58 under
35 U.S.C. § 103(a) as being rendered obvious by the combination of
Doytcheva and Zainuddin as 31, 34-37, 40, and 56-58, but reverse as to
claims 38, 39, 52, and 53.
We reverse the rejection of claims 41, 43, 46-51, 54 and 55 stand
under 35 U.S.C. § 103(a) as being rendered obvious by the combination of
Doytcheva and Froix.

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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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