Ex Parte Zeng et al

Patent Trials and Appeals Board

Apr 22, 2019

14986774 - (D) (P.T.A.B. Apr. 22, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
14/986,774 01/04/2016
121974 7590 04/24/2019
KACVINSKY DAISAK BLUNI PLLC
America's Cup Building
50 Doaks Lane
Marblehead, MA 01945
FIRST NAMED INVENTOR
Hongxia Zeng
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.
8150BSC0319 5712
EXAMINER
VU, JAKE MINH
ART UNIT PAPER NUMBER
1618
NOTIFICATION DATE DELIVERY MODE
04/24/2019 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):
bbonneville@kdbfirm.com
docketing@kdbfirm.com
ehysesani@kdbfirm.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte HONGXIA ZENG, STEVEN L. KANGAS, and
YEN-LANE CHEN 1
Appeal2018-005545
Application 14/986,774
Technology Center 1600
Before ERIC B. GRIMES, JEFFREY N. FRED MAN, and
TIMOTHY G. MAJORS, Administrative Patent Judges.
GRIMES, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to
microspheres that include paclitaxel, which have been rejected as obvious.
We have jurisdiction under 35 U.S.C. § 6(b ).
We reverse.
1 Appellants identify the Real Party in Interest as Boston Scientific Scimed,
Inc. Appeal Br. 3.
Appeal2018-005545
Application 14/986, 77 4
STATEMENT OF THE CASE
Claims 21, 23, 25, and 26 are on appeal. Claim 21 is illustrative and
reads as follows:
21. A polymer micro sphere consisting essentially of poly-
lactide-co-glycolide 50:50 (PLGA) and paclitaxel (Ptx), both
being distributed throughout the microsphere, and configured to
release Ptx in vitro in an initial burst lasting no more than
approximately two days, followed by a steady-state release
lasting approximately 15-20 days, wherein the PLGA consists
essentially of PLGA having an average molecular weight of
about 5,600 Daltons and PLGA having an average an average
[sic] molecular weight of about 16,000 Daltons.
Appeal Br. 12 (Claims Appendix).
Claim 23 is the other independent claim and is directed to the same
polymer microsphere defined by claim 21, with the additional requirement
that "the PLGA consists essentially of equal parts PLGA having an average
molecular weight of about 5,600 Daltons and PLGA having an average
molecular weight of about 16,000 Daltons." Id. (emphasis added).
DISCUSSION
The Examiner has rejected claims 21, 23, 25, and 26 under 35 U.S.C.
§ 103(a) as obvious based on Liggins. 2 Final Rej. 3 4. The Examiner finds
that Liggins teaches a microparticle "consisting essentially of: poly-lactide-
2 Liggins et al., WO 2006/002365 A2, published Jan. 5, 2006.
3 Office Action mailed June 7, 2017, which states that "[c]laims 1-3, 8-9, 21-
26 is/are rejected under 35 U.S.C. 103 as being unpatentable over LIGGINS
... for reasons of record in the previous office action filed on 02/24/2017."
Final Action 4.
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Appeal2018-005545
Application 14/986, 77 4
co-glycolide 50:50 (PLGA) and paclitaxel (see pages 95 and 99), wherein
the molecular weight of the PLGA is 7900 (see pg. 99)." Non-Final Action
5. 4 The Examiner also finds that Liggins teaches "drug release ha[ ving] an
initial burst lasting no[] more than approximately two days, followed by a
steady-state release lasting approximately 15-20 days (see chart on front
page)." Id.
The Examiner acknowledges that the "reference[] do[ es] not
specifically teach using the specific molecular weight of PLGA as claimed."
Id. at 6. The Examiner reasons, however, that
[ s ]ince all the polymers are PLGAs, the true average molecular
weight of the PLGAs in the microsphere composition is
between about 5,600-16,000 Daltons, since we don't know the
exact number of PLGA polymers in the 1st PLGAs and the 2nd
PLGAs to calculate the exact average molecular weight of total
PLGAs. Thus, Appellant's claim[s] actually recite a range for
average molecular weight to be between "about 5,600-16,000
Daltons".
Ans. 7. The Examiner points to Liggins' exemplary composition "consisting
of 50/50 PLGA polymers and having an average molecular weight of 7,900
Dalton." Id.
The Examiner also reasons that
[t]he molecular weight of the PLGA in a composition is clearly
a result effective parameter that a person of ordinary skill in the
art would routinely optimize .... It would have been customary
for an artisan of ordinary skill to determine the optimal
molecular weight of PLAGA [sic] in order to best achieve the
desired results, such as drug release rate.
Non-Final Action 6.
4 Office Action mailed Feb. 24, 2017.
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Application 14/986, 77 4
Appellants argue, among other things, that "because there is no
teaching or suggestion in Liggins to provide microparticles with a release
profile like that claimed, there would be no reason to optimize the molecular
weight of the PLGA to achieve this result." Appeal Br. 9. Appellants argue
that "picking and choosing from various ranges in various scenarios in the
prior art in order to arrive at a release profile having initial burst lasting no
more than approximately two days followed by a steady-state release lasting
approximately 15-20 days as claimed is not evidence of obviousness, but
rather of improper hindsight." Reply Br. 9. Appellants also point out that the
figure on the front page of Liggins, which the Examiner cites as showing the
claimed release profile, "corresponds to release from PLLA [poly(L-lactide)]
rather than PLGA as claimed." Id.
Appellants also argue that,
instead of a "true average molecular weight" of the PLGAs in
the microsphere composition, Applicant is claiming a mixture
two~ of poly-lactide-co-glycolide 50:50 (PLGA): (a) a first
PLGA having an average molecular weight of about 5,600
Daltons and (b) a second PLGA having an average an average
[sic] molecular weight of about 16,000 Daltons.
Reply Br. 12. Appellants point to the Specification's Figure 2 as evidence
that
a dramatic change in release profile occurs as one proceeds
from (a) 100% PLGA having an average molecular weight of
about 5,600 Daltons to (b) a mixture of 50% PLGA having an
average molecular weight of about 5,600 Daltons and 50%
PLGA having an average an average [sic] molecular weight of
about 16,000 Daltons to ( c) 100% PLGA having an average an
average [sic] molecular weight of about 16,000 Daltons. Thus,
a very real effect is achieved by mixing the two types of PLGA.
Id. at 13.
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Appeal2018-005545
Application 14/986, 77 4
We agree with Appellants that the Examiner has not shown that the
products of the claims on appeal would have been obvious to a person of
ordinary skill in the art, viewing Liggins without the benefit of hindsight. As
Appellants point out, the claims require microspheres consisting essentially
of paclitaxel and two different types of PLGA copolymers: a population of
PLGA copolymers with an average molecular weight of about 5600 Daltons,
and a population of PLGA copolymers with an average molecular weight of
about 16,000 Daltons. The Specification discloses that microspheres having
a 50:50 mixture of these types of PLGA copolymers "were characterized by
both burst release and about 15 days of steady-state release." Spec. ,r 24. See
also id. at ,r 12, Fig. 2.
Liggins discloses "microspheres having a high loading (i.e., higher
than 50% w/w) of one or more bioactive agents." Liggins 2. The bioactive
agent (drug) can be paclitaxel. Id. at 4. "In addition to a drug, the
microparticles ... also comprise a polymer." Id. at 35. The polymer can be
PLGA. Id. at 36. Liggins states that
[p ]olymers may have weight average molecular weights, for
example, of less than about 75,000 g/mol, or less than about
50,000 g/mol, or less than about 25,000 g/mol, or less than
about 10,000 g/mol, or less than 5000 g/mol. Representative
examples of polymers that can be synthesized with Mw falling
below 100,000 include ... PLGA.
Id. at 36-37.
Liggins exemplifies paclitaxel-containing microparticles made of
"50/50 PLGA." Id. at 95 (Table 4). Liggins also exemplifies paclitaxel-
containing microparticles made of "50/50 PLGA (MW 7900)," stabilized
with 10% w/v polyvinyl alcohol (PV A). Id. at 99 (Table 7). Liggins reports
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Appeal2018-005545
Application 14/986, 77 4
that the release profile over 15 days of"[ m ]icrospheres made with PLLA
(MW = 2000) ... having loadings of 40, 70, and 90% w/w paclitaxel" are
shown in its Figure 1 (i.e., the figure reproduced on Liggins' front page),
while "the release profile for 70% paclitaxel loaded PLLA 1200, 2000, and
45,000 microparticles" are shown in its Figure 2. Id. at 109. Liggins does not
report release profiles for paclitaxel-containing microparticles made of
PLGA.
Thus, while Liggins discloses paclitaxel-containing microspheres
made of 50:50 PLGA, it does not disclose making such microspheres with a
mixture of PLGA having an average MW of about 5,600 Daltons and PLGA
having an average MW of about 16,000 Daltons, as required by the claims
on appeal.
Nor has the Examiner identified a reason, based on Liggins, that
would lead a skilled artisan to choose the mixture of PLGA molecular
weights that is recited in the claims. While the Examiner reasons that a
skilled artisan would arrive at the claimed mixture of PLGAs based on
routinely optimizing "to best achieve the desired results, such as drug release
rate" (Non-Final Action 6), the Examiner does not point to any disclosure in
Liggins to show that the release profile recited in the claims, and resulting
from the claimed PLGA mixture, would have been recognized as desirable.
Liggins discusses possible release profiles of agents from its
microparticles but does not state that an initial burst of less than two days,
followed by steady-state release for fifteen to twenty days, is desirable, or
specifically that it is desirable for paclitaxel. Rather, Liggins states that its
"[ m ]icroparticles ... may have a wide[ ]range of release characteristics
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Appeal2018-005545
Application 14/986, 77 4
depending on the composition." Liggins 65. Liggins states that its
"microparticles release one or more therapeutic agents over a period of
several hours ... to days ... to months." Id. Liggins also states that
Id.
[ t ]he release profile may be characterized by the extent of its
burst (initial) phase .... [M]icroparticles may be defined as
"low" or "high" burst systems. For example, low burst systems
may release as little as about 30, 20, 10 or even 5 or 1 % of the
total amount loaded in the initial phase of release. High burst
systems may release at least about 50, 60, 70 or even 100% of
the total amount of drug in the burst phase .... For
microparticles intended to release over several days, the burst
phase may on the order of hours (e.g., 1 to 24 hours). For
microparticles intended to release over several weeks, the burst
phase may be from several hours to several days (e.g., 12 hours
to 7 days).
Liggins states that "high load 5-fluororacil [sic, 5-fluorouracil] or
mycophenolic acid microspheres made of a relatively hydrophilic polymer
will have a high burst and release all of the drug within several hours to a
few days." Id. "Alternately, paclitaxel loaded poly(lactide) microspheres
embedded in a PEG-based hydrogel scaffold, may release only a small
fraction of the total dose over 5 days, with a very small burst phase." Id. at
65---66. Liggins does not disclose that mixing different average molecular
weights of the same ( co )polymer ( e.g., PLGA) will affect the release of an
agent from microspheres made of the mixed ( co )polymer, in either the burst
phase or in sustained release.
In summary, the Examiner has not pointed to evidence provided by
Liggins that would lead a skilled artisan to desire the release profile recited
by the claims on appeal, or that would lead a skilled artisan to expect that
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Appeal2018-005545
Application 14/986, 77 4
mixing PLGA copolymers with different average molecular weights would
be effective in achieving the recited release profile.
With regard to the Examiner's position (Ans. 7) that the overall
average molecular weight of the PLGA copolymers recited in the claims
could be 7900 Daltons, and therefore the same as one of the PLGAs
exemplified by Liggins, the Examiner has not pointed to evidence showing
that the release profile of micro spheres made of a single copolymer having a
medium average molecular weight is the same as that of microspheres made
of two copolymers having different (high and low) average molecular
weights, even if the overall average molecular weight of the mixed
copolymers is the same as that of the single copolymer.
We therefore agree with Appellants (Appeal Br. 10) that the rejection
on appeal relies on impermissible hindsight. We reverse the rejection of
claims 21, 23, 25, and 26 under 35 U.S.C. § 103(a) based on Liggins.
REVERSED
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