Ex Parte Kuzma et al

Patent Trial and Appeal Board

Jun 28, 2016

12814276 (P.T.A.B. Jun. 28, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
12/814,276 06/11/2010 Petr KUZMA
105159 7590 06/30/2016
Ratner Prestia
P.O. Box 980
Valley Forge, PA 19482
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.
EPSI-107US1 8906
EXAMINER
REYNOLDS, FRED H
ART UNIT PAPER NUMBER
1675
NOTIFICATION DATE DELIVERY MODE
06/30/2016 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):
PCorrespondence@ratnerprestia.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte PETR KUZMA and STEPANIE DECKER 1
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Technology Center 1600
Before ULRIKE W. JENKS, JOHN G. NEW, and RYAN H. FLAX,
Administrative Patent Judges.
NEW, Administrative Patent Judge.
DECISION ON APPEAL
1 Appellants state the real parties-in-interest is Endo Pharmaceuticals
Solutions Inc. App. Br. 2.
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SUMMARY
Appellants file this appeal under 35 U.S.C. § 134(a) from the
Examiner's Final Rejection of claims 1-9, 11-13, and 15-23. Specifically,
claims 1-9, 11-13, 19, and 21-23 stand rejected as unpatentable under
35 U.S.C. § 103(a) as being obvious over the combination of Bodmer et al.
(US 5,538,739, July 23, 1996) ("Bodmer") and Kuzma et al. (US 5,266,325,
November 30, 1993) ("Kuzma").
Claims 1, 17, and 18 also stand rejected as unpatentable under
35 U.S.C. § 103(a) as being obvious over the combination ofBodmer,
Kuzma, and Wilbur (US 3,772,435, November 13, 1973) ("Wilbur"). 2
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
NATURE OF THE CLAIMED INVENTION
Appellants' invention is directed to a formulation of octreotide or
pharmaceutically acceptable salts thereof, which provides controlled release
of a therapeutically effective amount of octreotide for a period of at least
about two months. Methods of treating acromegaly, decreasing growth
2 Claims 10 and 14 are canceled. App. Br. 12. Claims 15, 16, and 20 are
listed as rejected on form PTOL-326 of the Final Office Action. See Final
Act. 1. Therefore, Appellant was placed on notice that these claims stood
rejected. While the Examiner's Final Rejection states no Ground of
Rejection for these claims, nor are they argued separately in Appellants'
Appeal Brief or the Examiner's Answer, because all pending claims were
rejected by the Examiner in the Final Action, and because claims 15, 16, and
20 depend from claim 1, which has been rejected by the Examiner in both of
the§ 103 final rejections, we consider these claims rejected and argued
together with claims 1-9, 11-13, 19, and 21-23.
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hormone, decreasing IGF-1, and treating conditions associated with
carcinoid tumors and VIPomas by administering a controlled release
formulation of octreotide. Abstract.
REPRESENTATIVE CLAIM
Claim 1 is representative of the claims on appeal and recites:
1. A method of treating a patient suffering from a condition
associated with carcinoid tumors or suffering from one or more
symptoms associated with such condition, the method
compnsmg:
implanting subcutaneously into a patient in need thereof
at least one implant comprising a hydrophilic polymer and a
pharmaceutical formulation comprising octreotide;
wherein the hydrophilic polymer comprises a copolymer
of at least two hydrophilic, ethylenically unsaturated
monomers;
wherein the hydrophilic polymer has an equilibrium
water content ranging from about 20% to about 75%;
wherein the pharmaceutical formulation is contained
within the hydrophilic polymer;
wherein the pharmaceutical formulation contains
between about 20 to about 150 milligrams of octreotide, in free
form or salt form; and
wherein the at least one implant releases a therapeutically
effective amount of the octreotide to the patient over a period of
at least about two months.
App. Br. 11.
ISSUES AND ANALYSES
We agree with, and adopt, the Examiner's findings and conclusion
that the appealed claims are prima facie obvious over the cited prior art
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references. We address the arguments raised by Appellants on appeal
below.
A. Claims 1-9, 11-13, 19, and 21-23
Issue
Appellants argue the Examiner erred because the modification
asserted by the Examiner would change the principle of operation of the
prior art invention and render that invention unsuitable for its intended
purpose. App. Br. 4.
Analysis
Appellants assert that Bodmer teaches a sustained release formulation
"in a biodegradable and biocompatible polymeric carrier ... in the form of
a[ n] implant or preferably a microparticle." App. Br. 4 (quoting Bodmer
col. 1, 11. 13-19). Furthermore, Appellants contend, Bodmer teaches that the
polymer of the implant should be formulated to "[lead] to a controllable
biodegradation rate of the polymer ... and to a corresponding sustained
release of the peptide, which make a depot formulation made therefrom
suitable for e.g.[,] a one month's release." Id. at 5 (quoting Bodmer col. 8,
11. 30-34).
Appellants point to the Declaration of their expert, Scot Thoroughman
(the "Thoroughman Declaration"), in which, they argue, Mr. Thoroughman
declares that such an implant is known in the art as a depot implant or
matrix-loaded implant in which the active principle is dispersed throughout a
polymer matrix. App. Br. 5 (citing Thoroughman Deel. 3). Mr.
Thoroughman also explains that such depot implants provide a first-order
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release profile as the release of the active principle depends on the
degradation of the polymer; which results in drug release that changes over
time. Id.
In contrast, Appellants argue, Kuzma teaches the use of an implant
that "is biocompatible and non-toxic to the host and non-biodegradable."
App. Br. 5 (citing Kuzma col. 15, 11. 37-39). Appellants assert Kuzma
further teaches that because the implant is nonbiodegradable, it is "amenable
to long term implantation since degradation products are not dispersed
throughout the body." Id. (quoting Kuzma col. 15, 11. 37-39). Appellants
explain that the Thoroughman Declaration declares that such non-
biodegradable implants are known in the art as reservoir-loaded implants,
which exhibit a zero-order release profile because the release rate of the
active principle is substantially constant. Id. (citing Thoroughman Deel. 2-
3).
Appellants argue that modifying the biodegradable implant of Bodmer
to use a non-biodegradable implant taught by Kuzma, as suggested by the
Examiner, would change the principle of operation of the invention of
Bodmer because such a modification would change how the active principle
is delivered to the patient. App. Br. 5. Appellants also argue the
combination of the references would render the invention of Bodmer
unsuitable for its intended purpose by replacing a biodegradable implant
with "a controllable biodegradation rate of the polymer ... and to a
corresponding sustained release of the peptide" with a nonbiodegradable
implant that avoids "degradation products [being] dispersed throughout the
body." Id. at 6 (quoting Bodmer col. 8, 11. 24--34; Kuzma col. 15, 11. 37-39).
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The Examiner responds that both Bodmer and Kuzma address the
problem of the less desirable pharmacokinetics of drugs applied without
sustained release formulations, and both references teach the use of an
implant to solve this problem. Ans. 6 (citing Bodmer col. 1, 11. 23-30; 31-
36; Kuzma col. 2, 11. 37--40; 16-21). The Examiner acknowledges that
Bodmer and Kuzma teach different types of implants to solve the problem,
however both references teach improving the delivery pharmacokinetics of
therapeutic drugs, and the principle of operation of both references is the
controlled release of the therapeutic agent via a polymeric implant. Id.
The Examiner finds the Thoroughman Declaration, apart from
providing Mr. Thoroughman's credentials and opinions, does not provide
any new facts or arguments, but merely re-presents arguments and facts
already present in the record. Ans. 6-7.
We are not persuaded by Appellants' arguments. Both of the cited
prior art references teach drug delivery systems which rely on implants.
Bodmer teaches:
This invention relates to sustained release formulations, e.g.[,]
microparticle formulations, of a drug, especially of a hormonally
active water-soluble somatostatin or a somatostatin analog such
as octreotide, providing a satisfactory drug plasma level and,
e.g.[,] in a biodegradable, biocompatible polymer, e.g.[,] in a
encapsulating polymer matrix. The polymer matrix may be a
synthetic or natural polymer.
Bodmer col. 3, 11. 30-36. Kuzma teaches:
[T]he invention relates to water-insoluble, water-swellable,
homogenous hydrogel copolymers of 2-hydroxyethyl
methacrylate (HEMA) and at least one ethylenically unsaturated
hydrophilic monomer copolymerizable therewith which are
especially adaptable for use in drug delivery devices such as
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body implants whereby the contained drug is diffused through
the hydrogel copolymer membrane to the body environment at a
predetermined rate.
Kuzma col. 1, 11. 20-29. We therefore agree with the Examiner that both
references teach implant-based drug delivery systems. Although Appellants'
point that the references teach implants with different properties (i.e.,
biodegradable vs, nonbiodegradable) is correct, Appellants have provided
insufficient reasoning to overcome the Examiner's prima facie conclusion
that a person of ordinary skill in the art, in light of the teachings of both
references would find it obvious to combine the implant-based delivery of
octreotide (as taught by Bodmer) via a non-biodegradable implant (as taught
by Kuzma) to obtain the predetermined drug delivery rate taught by Kuzma.
Similarly, the Thoroughman Declaration fails to overcome the
Examiner's conclusion of obviousness. Mr. Thoroughman opines that:
"[S]ubstituting the non-biodegradable reservoir implant of Kuzma for the
biodegradable matrix depot implant of Bodmer would not have been obvious
to one of ordinary skill in the art as both the technology used to develop, and
the principle of operation for, the implant classifications differ
significantly." Thoroughman Deel. 2. After explaining the difference
between the implants taught by Bodmer and Kuzma, Mr. Thoroughman
declares further that:
Substituting a non-biodegradable implant membrane for a
biodegradable implant membrane, as required in the
modification suggested by the Examiner, would therefore change
the principle of operation of the implant of Bodmer because the
active principle would be released in a completely different
manner (i.e.[,] zero-order release profile vs. first-order release
profile) leading to release rate characteristics unlikely to yield a
viable extended release drug product.
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Thoroughman Deel. 3.
As an initial matter, Mr. Thoroughman has an M.S. degree in
Chemistry and (as of the date of the Thoroughman Declaration) has multiple
years of experience in the field of body implants, the last five of which as
Director of AR&D, a senior role responsible for analytical characterization
of non-biodegradable implant technologies within the Implant Drug
Delivery group at Endo Pharmaceutical Solutions, Inc., the assignee of the
instant application. Thoroughman Deel. 1. We therefore find Mr.
Thoroughman to be a credible expert witness in the field of drug implant
delivery systems. However, obviousness is a conclusion of law and, because
he lacks any legal training, we assign little probative value to Mr.
Thoroughman's conclusion of obviousness quoted supra.
Moreover, although we accept Mr. Thoroughman's statements that the
drug delivery systems of Bodmer and Kuzma might operate differently,
Mr. Thoroughman does not opine or offer evidence that the drug delivery
system taught by Kuzma could not be used to deliver the drug octreotide, as
taught by Bodmer. Nor does he opine or offer evidence that, in delivering
octreotide, the purpose of the implant of Kuzma would somehow be altered
or its disclosed device rendered unfit for its intended purpose. We agree that
the pharmacodynamics of delivery could be different using the implant of
Kuzma versus that taught by Bodmer, but neither Mr. Thoroughman nor
Appellants adduce evidence that such differences would not be obvious to a
person of ordinary skill in the art.
The test for obviousness "is what the combined teachings of the
references would have suggested to those of ordinary skill in the art." In re
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Keller, 642 F.2d 413, 425 (C.C.P.A. 1981). Furthermore, "[t]he
combination of familiar elements according to known methods is likely to be
obvious when it does no more than yield predictable results." KSR Int 'l Co.
v. Teleflex Inc., 550 U.S. 398, 416 (2007).
We agree with the Examiner's conclusion that it would have been
obvious to combine the teachings of Bodmer and Kuzma so as to deliver
octreotide, which Bodmer teaches can be delivered via an implant, via the
nonbiodegradable implant of Kuzma. The combination would have the
predictable result of delivering the therapeutic agent "to the body
environment at a predetermined rate." See, e.g., Thoroughman Deel. 3
("The performance of the current generation of non-biodegradable implants
sacrifice ease of administration and the requirement for post-treatment
surgical implant retrieval for improvements in the duration of treatment and
consistency of release rate"). We consequently affirm the Examiner's
rejection of the claims.
B. Claims 1, 17, and 18
Appellants argue these claims separately, but advance the same
arguments presented with respect to claims 1-9, 11-13, 19, and 21-23.
App. Br. 8-9. For the same reasons set forth above, we affirm the
Examiner's rejection of claims 1, 17, and 18.
DECISION
The Examiner's rejection of claims 1-9, 11-13, and 15-23 as
unpatentable under 35 U.S.C. § 103(a) is affirmed.
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No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(l). See 37 C.F.R.
§ 1.136(a)(l )(iv).
AFFIRMED
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