Ex Parte Hasirci et al

Patent Trial and Appeal Board

May 24, 2016

10886851 (P.T.A.B. May. 24, 2016)

UNITED STATES PATENT AND TRADEMARK OFFICE
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
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
10/886,851 07/08/2004 Vasif N. Hasirci TEPH 108 2159
23579 7590 05/25/2016
Pabst Patent Group LLP
1545 PEACHTREE STREET NE
SUITE 320
ATLANTA, GA 30309
EXAMINER
WESTERBERG, NISSA M
ART UNIT PAPER NUMBER
1618
MAIL DATE DELIVERY MODE
05/25/2016 PAPER
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.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte VASIF N. HASIRCI and DILEK SENDIL KESKIN1
__________

Appeal 2013-008725
Application 10/886,851
Technology Center 1600
__________

Before JEFFREY N. FREDMAN, JOHN G. NEW, and
ROBERT A. POLLOCK, Administrative Patent Judges.

POLLOCK, Administrative Patent Judge.

DECISION ON APPEAL
Appellants appeal under 35 U.S.C. § 134(a) from the final rejection of
claims 1, 3–6, 8, 9 and 12–19.2 We have jurisdiction under 35 U.S.C. § 6(b).
We affirm.
STATEMENT OF THE CASE
“Polyhydroxyalkanoates (PHAs) are a class of naturally occurring
polyesters that are synthesized by numerous organisms in response to
environmental stress.” Spec. 4:29–31. For example, in bacteria, PHA

1 Appellants identify the Real Parties in Interest as Tepha, Inc. and Bard
Shannon Limited. App. Br. 2.
2 Although repeatedly referenced in the Examiner’s Answer, claim 2 is not
pending in this Appeal. See Final Rejection dated July 24, 2012, page 1.
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polymers may accumulate up to 90% by dry weight in response to nutrient
limitation and serve as carbon and energy reserve materials. Id. at 5:29–32.
These biodegradable polymers have been used to produce a range of medical
devices and drug delivery systems, including controlled release systems. Id.
at 9:18–19, 9:28–10:2. Copolymers of the PHAs 4-hydroxybutyrate and 3-
hydroxybutyrate have been used to develop drug delivery systems. Id. at
9:28–31. Homopolymers of 4-hydroxybutyrate—poly-4-hydroxybutyrate
(“referred to as PHA4400 or P4HB”)—form “a strong, pliable
thermoplastic” that has been used to make, “compression molded porous
samples, fibers, foams, coated meshes, and microspheres.” Id. at 4:2–3, 19–
28, 10:2–4.
The Specification discloses the use of PH4B in drug delivery systems
for a “protein, peptide, polysaccharide, nucleic acid molecule, or synthetic or
natural organic compound” in “virtually any form, including granules,
sheets, films, and particles, such as microspheres, nanospheres,
microparticles, and microcapsules, as well as molded forms, such as patches,
tablets, suspensions, pastes, rods, disks, pellets, and other molded forms.”
Id. at 8:13–25, 11:13–26.
In Example 1 of the Specification, neutral tetracycline (TC), or
tetracycline HCl (TCN) blended with PH4B (“Mw ~450 K”) in various
ratios was formed into 2x5x5 mm rods. Id. at 12:10–25. Drug release from
the tetracycline-loaded rods was determined by shaking the material at 37°C
in “a 50 mL Falcon tube containing 30 mL of 0.1 M pH 7.4 PBS (phosphate
buffer),” with daily replacement of the release buffer. Id. at 12:26–13:17
(Example 2). In an embodiment having a 2:1 ratio of polymer:drug by
weight, “[t]he average cumulative release of TC at 11 days was
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approximately 25% versus 9% for TCN, demonstrating long term or
sustained release.” Id. at 13:7–8.
Independent claim 1 is illustrative and reads as follows (paragraphing
added):
1. A biodegradable controlled release drug delivery system
comprising
drug uniformly distributed in a 4-hydroxybutyrate
homopolymer at a percent loading of up to 50% by weight
of the drug delivery system,
wherein the 4-hydroxybutyrate homopolymer has a
weight average molecular weight of 50,000 to 1,000,000
daltons,
wherein in an in vitro assay, the drug delivery system
releases less than 60% of the drug uniformly distributed
therein, within ten days.
Claims 1, 3–5, 9, and 12–19 stand rejected under 35 U.S.C. § 103(a)
as unpatentable in view of Williams.3
Claims 1, 3, 4, 6, 8, 9, and 12–19 stand rejected under 35 U.S.C.
§ 103(a) as unpatentable in view of Martin.4
Claims 1, 3–6, 8,5 9, and 12–19 stand rejected under 35 U.S.C.
§ 103(a) as unpatentable in view of Williams as applied to claims 1–5, 9,
and 12–19, above, and further in view of Martin.

3 Williams and Martin, WO 01/19361 A2, published March 22, 2001.
4 Martin et al., WO 99/32536 A1, published July 1, 1999.
5 The omission of claim 8 in the Final Rejection appears to be a
typographical error as it appears at page 7 of the Examiner’s Answer and
page 23 of Appellant’s Reply Brief.
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Claims 5 stands rejected under 35 U.S.C. § 103(a) as unpatentable in
view of Martin as applied to claims 1–4, 6, 8, 9, and 12–19, above, and
further in view of Gursel.6
ANALYSIS
We have reviewed Appellants’ contentions that the Examiner erred in
rejecting claims 1, 3–6, 8, 9 and 12–19 as unpatentable over the cited art.
App. Br. 8–37; Reply Br. 3–28. We disagree with Appellants contentions
and adopt the findings concerning the scope and content of the prior art set
forth in the Examiner’s Answer and Final Rejection dated July 24, 2012.
For emphasis, we highlight and address the following:
Williams
FF1. Williams teaches the administration of gamma-hydroxybutyrate (GHB
or 4-hydroxybutyrate) for the treatment of a wide variety of conditions
including narcolepsy, schizophrenias, and myocardial infarction. See
e.g., Williams, Abstract, 1:11–4:29. Williams teaches that sustained
blood levels of GHB may be obtained by administering polymers or
oligomers of GHB, which release the monomer over time as the polymer
or oligomer is metabolized, thereby reducing the need for frequent
administration. Id. at 6:7–15, 10:3–8. “The preferred compositions may
contain GHB alone, as in a homopolymer (or oligomer) of gamma-
hydroxybutyrate, or may comprise GHB in a polymer or oligomer
together with other monomers.” Id. at 8:17–19. The compositions can
also include other therapeutics or prophylactic agents . . . [including]

6 Gursel et al., In vitro antibiotic release from poly(3-hydroxybutyrate-co-3-
hydroxyvalerate) rods, 19(2) J. MICROENCAPSULATION 153–164 (2002).
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“compounds having anti-microbial activity, anesthetics, adjuvants,
antiinflammatory compounds, stimulants, antidepressants, surfactants,
steroids, lipids, enzymes, antibodies, and hormones.” Id. at 10:23–28.
FF2. Williams Example 1 discloses a GHB homopolymer having a MW of
430,000 degraded using sodium methoxide to polymers having a
molecular mass of 320,000, 82,000, and 25,000 respectively. Id. at 12:1–
13. Williams Example 2 shows that rats gavaged with GHB monomer
had undetectable blood levels of GHB after 6 hrs, whereas animals
gavaged with the 25,000 MW GHB homopolymer had serum
concentrations of GHB of 3–5 fold over baseline values for over 10
hours, thereby indicating that the homopolymer “provides a sustained
release of the monomer, over at least 10 hours.” Id. at 13:20–14:5.
Martin
FF3. Martin discloses “Biocompatible polyhydroxyalkanoate compositions,
particularly based on biotechnologically produced homo- and copolymers
of 4- hydroxybutyric acid, with controlled degradation rates.” Martin,
Abstract. In a preferred embodiment, the polymers have a molecular
weight of 10,000 to 10,000,000 Daltons. Id. at 7:4–7.
FF4. Martin teaches that the polymer compositions “may contain or be
modified to include other molecules, such as bioactive and detectable
compounds” (id. at 7:8–12) including “cell attachment factors, growth
factors, peptides, and antibodies” (id. at 19:30–20:4; see id. at 18:19–
20:9) and “are useful for preparing a variety of biodegradable medical
devices. The biodegradable polymers preferably exhibit a relatively slow
biodegradation, for example, having a in vivo half-life of between three
and six months or less.” (id. at 17:26–29).
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In the case of controlled release, a wide range of different
bioactive compounds can be incorporated into a controlled
release device. These include hydrophobic, hydrophilic, and
high molecular weight macromolecules such as proteins. The
bioactive compound can be incorporated into the PHAs in a
percent loading of between 0.1 % and 70% 20 by weight,
more preferably between 5% and 50% by weight. The PHAs
may be in almost any physical form, such as a powder, film,
molded item, particles, spheres, latexes, and crystalline or
amorphous materials . . . . are suitable for use in applications
requiring slowly degrading, biocompatible, moldable
materials, for example, medical devices [including] “stents,
tissue engineering devices, [and] drug delivery devices.
Id. at 19:15–29.
In rejecting claims 1–5, 9, and 12–19 over Williams, the Examiner
finds that it would have been obvious to prepare a drug delivery system
incorporating GHB homopolymer (i.e., the claimed “4-hydroxybutyrate
homopolymer,” or P4HB) and an additional therapeutic agent relevant to the
particular condition being treated. Ans. 4. The Examiner further finds that
polymer size,7 the amount of therapeutic agent, as well as release time and
release profile, are result effective parameters that a person of ordinary skill
in the art would routinely optimize with a reasonable expectation of success.
Id. at 5–6. Accordingly, the Examiner concludes, it would have been
obvious “to determine the optimal polymer size in order to best achieve the
desired results based on the desired levels of GHB and length of time over

7 We agree with the Examiner’s determination that one of ordinary skill in
the art would understand that the molecular weight of a polymer
composition, including a PHA polymer composition, is a result effective
variable with respect to biodegradation, and thus, drug release rate. See Fin.
Rej. 5 (referencing, e.g., Martin 13:27–30, and Goldberg (US 5,085,629)
claim 25).
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which the release occurred and the therapeutic dosage and release time of
the additional therapeutic agents.” Id. at 5. With respect to the structure of
claimed drug distribution system, the Examiner concludes that it would have
been obvious to uniformly distribute the therapeutic agent in the GHB
homopolymer “as this will allow for decreased variability of drug content
from one device to another.” Id. at 5–6; see Fin. Rej. 5.
Appellants argue that the Examiner errs in rejecting claims 1–5, 9, and
12–19 over Williams because Williams is directed to using a homopolymer
of 4-hydroxybutyrate to deliver 4-hydroxybutyrate monomers, but does not
contemplate using the polymeric matrix to provide controlled release
delivery of any other drug; and that Williams does not contemplate that such
drug comprises up to 50% by weight of the drug delivery device, is
uniformly distributed in a homopolymer of 50,000 to 1,000,000 MW, or that
less than 60% of the drug is released within ten days. Ans. 10–15, 22. We
do not find Appellants’ arguments persuasive.
With respect to the argument that Williams does not contemplate
using the biodegradable homopolymers to provide controlled release
delivery of any drug other than 4-hydroxybutyrate, we note that Williams
discloses compositions comprising biodegradable homopolymers of 4-
hydroxybutyrate that are metabolized over time to provide sustained (i.e.
controlled) release of 4-hydroxybutyrate monomers, and optionally include
other therapeutics. FFs. 1–2. “‘[I]t is elementary that the mere recitation of
a newly discovered function or property, inherently possessed by things in
the prior art, does not cause a claim drawn to those things to distinguish over
the prior art.’” In re Best, 562 F.2d 1252, 1254–55 (CCPA 1977) (quoting
In re Swinehart, 439 F.2d 210, 212–13 (CCPA 1971)).
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In the present case, Appellant does not demonstrate that the controlled
release of such additional therapeutics “in an in vitro assay” as presently
claimed, is not an inherent property of William’s compositions. See Fin.
Rej. 4 ( “The polymeric matrix provides for the controlled release of
materials that are present in the matrix itself, and so while Williams may not
describe the release profile of the additional agents in the matrix, the matrix
necessarily provides for controlled release of such agents. Applicants have
not provided any evidence that the drug release from the matrices disclosed
by Williams does not meet the release limitations.).
That the claimed controlled release properties are inherent in
William’s compositions is apparent from the breadth of the in vitro assay
recited in independent claim 1. Nowhere does the Specification define the
metes and bounds of such an assay, providing only a single embodiment that
involves shaking solid material at 37°C in “a 50 mL Falcon tube containing
30 mL of 0.1 M pH 7.4 PBS (phosphate buffer),” with daily replacement of
the release buffer. See Spec.12:26–13–17. Neither claim 1, nor any of its
dependent claims invoke this particular in vitro assay, and we find no reason
to import such limitations from the Specification. SuperGuide Corp. v.
DirecTV Enters., Inc., 358 F.3d 870, 875 (Fed. Cir. 2004) (“Though
understanding the claim language may be aided by the explanations
contained in the written description, it is important not to import into a claim
limitations that are not a part of the claim.”).
Applying the broadest reasonable construction in light of the
Specification, we interpret the language of claim 1, “wherein in an in vitro
assay, the drug delivery system releases less than 60% of the drug uniformly
distributed therein, within ten days,” as requiring the release of less than
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60% of the drug within ten days, using any in vitro assay.8 So construed, we
agree with the Examiner that one of ordinary skill would find it obvious to
optimize polymer size and drug loading parameters to achieve the claimed
invention with a reasonable expectation of success in achieving a drug
delivery system of the claimed composition that achieves 60% of drug
release within ten days using “an in vitro assay.”
We are also not persuaded by Appellants’ reliance on the declaration
of co-inventor, Dr. Simon F. Williams, which characterizes the 82,000 Da
molecular weight P4HB intermediates prepared according to Williams as
“lumps of plastic” “not suitable for use without further processing, for
example to remove unreacted product” and which, in contrast to Williams’
25,000 MW crystalline powder P4HB polymer, “would not be suitable for in
vivo administration.” App. Br. 19; Declaration under 37 C.F.R. § 1.132,
dated January 8, 2010 ¶4. Dr. Williams does not explain why “lumps of
plastic,” per se, are unsuitable for in vivo administration; the extent of
“further processing” required to render the polymers suitable for further use;
or how the 82,000 dalton 4-hydroxybutyrate homopolymers in Williams
differ from the 50,000 to 1,000,000 daltons 4-hydroxybutyrate
homopolymers recited in claim 1.
We further do not agree with Appellants’ argument that EP 0945137
teaches away from the selection of 4-hydroxybutyrate homopolymers. See
App. Br. 20–21; Reply Br. 10–11. On the available record, Appellant does

8 We agree with the Examiner’s reasoning that Appellants have not
demonstrated that the claimed release profile is unexpected in light of the
prior art. Ans. 14. Appellants’ failure to demonstrate unexpected results is
further underscored by the broad scope of the claimed “in vitro assay.”
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not convince us the Examiner errs in discounting the results in EP 0945137
because the reference tests release rates in a pH 1.2 solution and one of
ordinary skill in the art recognizes that the tested polymers are esters
sensitive to acid-catalyzed hydrolysis. See Ans. 11.
In rejecting claims 1–4, 6, 8, 9 and 12–19 over Martin, the Examiner
finds that it would have been obvious
to prepare a drug delivery device using P4HB as the matrix
material with a therapeutic agent incorporated therein. The
person of ordinary skill in the art would have been motivated
to make those modifications and reasonably would have
expected success because Martin et al. discloses these
materials as a suitable matric for various drug delivery
applications, including particles, stents and coatings on
medical devices. The amount of a specific ingredient (e.g.,
therapeutic agent) and molecular weight of the polymeric
matrix material are clearly result effective parameters that a
person of ordinary skill in the art would routinely optimize.
Optimization of parameters is a routine practice that would
be obvious for a person of ordinary skill in the art to employ
and reasonably would expect success. It would have been
customary for an artisan of ordinary skill to determine the
optimal amount of each ingredient to add in order to best
achieve the desired results of drug release in terms of amount
released and the time frame over which drug release occurs.
Ans. 6.
Appellants argue that the Examiner’s rejection is in error because
“Martin does not narrow down the list of polymers disclosed therein (the
complete universe of PHAs) to a finite list of predictable solutions, with
respect to what polymers can provide controlled and sustained release of a
drug” and thus, “one would not select P4HB as a polymer of choice with an
expectation of success in obtaining controlled and sustained delivery of a
drug loaded therein as required by claim 1.” App. Br. 27.
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We do not find Appellants’ argument persuasive. Martin discloses
“[b]iocompatible polyhydroxyalkanoate compositions, particularly based
on biotechnologically produced homo- and copolymers of 4-
hydroxybutyric acid, with controlled degradation rates.” FF. 3 (Martin,
Abstract (emphasis added)). Given this focus on 4-hydroxybutyric acid
polymers, we find no error in the Examiner’s conclusion that it would have
been obvious to use homopolymers of hydroxybutyric acid along with other
bioactive compounds in controlled release applications. See FF. 4.
Appellant also argues that Martin teaches altering polymer
degradation rates by increasing polymer porosity, “which would influence
drug release kinetics.” App. Br. 28–29. We note that the instant claims are
silent with respect to this variable and, in accord with page 6 of the Answer,
merely provides another means to optimize the control release compositions
disclosed in Martin. See Ans. 9. As noted by the Examiner, “[o]ptimization
of parameters is a routine practice that would be obvious for a person of
ordinary skill in the art to employ and reasonably would expect success.” Id.
at 6.
Appellants make similar arguments with respect to the rejections over
combination of Williams and Martin and Martin and Gursel. In sum, we
agree with the Examiner that one of ordinary skill reading Williams, Martin,
Martin and Williams, or Martin and Gursel would have found it obvious to
optimize the result effective parameters discussed above to achieve a drug
delivery system of the claimed composition, wherein 60% of drug was
released within ten days using “an in vitro assay,” with a reasonable
expectation of success.
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SUMMARY
The rejections of record are affirmed.
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