Ex Parte Chen et al

Patent Trial and Appeal Board

Jul 15, 2016

11278472 (P.T.A.B. Jul. 15, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
111278,472
31498 7590
Durect Corporation
10260 Bubb Road
Cupertino, CA 95014
0410312006
07118/2016
FIRST NAMED INVENTOR
GuohuaChen
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.
DURE-312 DIV 6429
EXAMINER
VU, JAKE MINH
ART UNIT PAPER NUMBER
1618
MAILDATE DELIVERY MODE
07/18/2016 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 GUOHUA CHEN and DAVID PRIEBE1
Appeal2014-006773
Application 11/278,472
Technology Center 1600
Before JEFFREYN. FREDMAN, RICHARD J. SMITH, and
TA WEN CHANG, Administrative Patent Judges.
CHANG, Administrative Patent Judge.
DECISION ON APPEAL
Appellants appeal under 35 U.S.C. § 134(a) involving claims to
methods of administering a beneficial agent to a subject comprising
providing an injectable depot composition, which have been rejected as
obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
STATEMENT OF THE CASE
According to the Specification, prior art polymer compositions for
injectable implants have used solvent or plasticizers that are relatively
1 Appellants identify the Real Party in Interest as Durect Corporation.
(Appeal Br. 3.)
Appeal2014-006773
Application 11/278,472
soluble in aqueous body fluids. (Spec. if 8.) Further according to the
Specification, when such implants are placed in the body and exposed to
aqueous body fluids they take up water rapidly, which often results in an
uncontrolled release of beneficial agent contained within the implant. (Id.)
The Specification states that the present invention "provides controlled
release of [a] beneficial agent to the subject being treated, the release being
controlled over a period equal to or less than two weeks after administration,
[preferably] a period of about 3 to about 7 days." (Id. if 12.)
Claims 11-14, 16, 18-20, 23-33, 37, and 39 are on appeal. Claim 11
is illustrative and reproduced below with key limitations emphasized:
11. A method of administering a beneficial agent to a subject,
compnsmg:
providing an injectable depot composition comprising:
(a) a bioerodible, biocompatible polymer having a weight
average molecular weight ranging from 3 000 to 9000;
(b) a solvent selected from the group consisting of
aromatic alcohols, esters of aromatic acids, aromatic ketones,
and mixtures thereof, said solvent having miscibility in water of
less than or equal to 7% at 25°C, and present in an amount from
about 95 to about 10% by weight, based on the combined weight
of the polymer and the solvent; and
( c) a beneficial agent; wherein said composition remains a
gel after implantation and the polymer and solvent are selected
to provide a composition that is sufficient to deliver the
beneficial agent in a controlled manner over a duration of less
than about seven days; and administering said composition to the
subject.
2
Appeal2014-006773
Application 11/278,472
The Examiner rejects claims 11-14, 16, 18-20, 23-33, 37, and 39
under 35 U.S.C. § 103(a) as being unpatentable over Brodbeck.2,3 (Ans. 2.)
DISCUSSION
Issue
The Examiner has rejected claims 11-14, 16, 18-20, 23-33, 37, and
39 under 35 U.S.C. § 103(a) as being unpatentable over Brodbeck. The
Examiner finds that Brodbeck teaches
a method of administering a beneficial agent to a subject comprising .
. . providing a gel composition comprising: 40-60% of a polymer,
such as a PLGA, which is a copolymer of lactic acid and glycolic
acid, with molecular weight of about 8,000-13,000, preferably 10,000;
50% of a solvent, such as benzyl benzoate; a beneficial agent, such as
hormone; and administering said composition to the subject.
(Final Act. 3 (citations omitted).) The Examiner further finds that Brodbeck
teaches delivery period of less than 7 days. (Id.)
The Examiner finds that Brodbeck does not "specifically teach the
specific polymer weight average molecular weight range ... claimed by
Applicant." (Id.) However, the Examiner finds that this limitation is
obvious because "[t]he weight average molecular weight of a polymer in a
composition is clearly a result effective parameter that a person of ordinary
skill in the art would routinely optimize." (Id.)
Appellants contend that Brodbeck does not disclose the weight
average molecular weight range of its polymers and only discloses number
2 Brodbeck et al., U.S. Patent No. 6,130,200, issued Oct. 10, 2000
("Brodbeck").
3 Claims 36 and 38 have been cancelled. (Amendment after Final Act. 6
(July 22, 2013).)
3
Appeal2014-006773
Application 11/278,472
average molecular weights, and also contend that the Examiner does not
have support for the conclusion that weight average molecular weight of the
polymer is a result effective parameter that a skilled artisan would optimize.
(Appeal Br. 7, 9.) Appellants additionally contend that, even if it were
obvious to use a polymer having a weight average molecular weight from
3000 to 9000, it would not have been obvious to "pick and choose from the
broad teachings of Brodbeck" to arrive at an embodiment having a delivery
period of less than 7 days, since such an embodiment is not preferred. (Id. at
9.) Finally, Appellants contend that the claims are non-obvious because the
claimed formulations "surprisingly provide a controlled, sustained release of
beneficial agent over a short duration of time." (Id. at 10.)
The issues with respect to this rejection are ( 1) whether Brodbeck
renders obvious the limitation of a polymer having a weight average
molecular weight ranging from 3000 to 9000 for use in an injectable depot
composition in a method of administering a beneficial agent to a subject; (2)
whether Brodbeck renders obvious an injectable depot composition having
the claimed components that deliver a beneficial agent in a controlled
manner over a duration of less than about seven days; and (3) whether the
claimed formulations provide unexpected results that, when weighed with
the evidence supporting the prima facie case, shows that the claimed
formulations would not have been obvious.
Findings of Fact
1. Brodbeck teaches " [ m] ethods and compositions for
systematically or locally administering ... a beneficial agent to a subject."
(Brodbeck Abstract.)
2. Brodbeck teaches an injectable gel composition comprising:
4
Appeal2014-006773
Application 11/278,472
A) mixing a biocompatible polymer and a solvent having a miscibility
in water of 7% or less selected from lower alkyl and aralkyl esters
of benzoic acid to form a viscous gel;
B) dispersing or dissolving a beneficial agent, optionally associated
with a solubility modulator of the beneficial agent, in an
emulsifying agent to form a beneficial agent containing
emulsifying agent; and
C) mixing the beneficial agent containing emulsifying agent with the
viscous gel, said beneficial agent containing emulsifying agent
forming a dispersed droplet phase in the viscous gel, and
optionally,
D) mixing one or more of a pore former and an osmotic agent with
said viscous gel.
(Brodbeck 6: 46-61.)
3. Brodbeck teaches solvent or solvent mixture present in an
amount of "from about 95 to about 20% by weight ... [,] preferably ... 70
to about 30% by weight and often 60-40% by weight of the viscous gel, i.e.,
the combined amounts of the polymer and the solvent." (Id. at 17:51-56.)
4. Brodbeck teaches that its gel compositions can provide
controlled release of the beneficial agent. (Id. at 1: 10-12.)
5. Brodbeck defines the term "prolonged period" to mean "a
period of time over which release of a beneficial agent from the implant of
the invention occurs, which will generally be about one week or longer, and
preferably about 30 days or longer." (Id. at 10:1--4.)
6. Brodbeck discloses poly(lactide-co-glycolide )copolymers, or
PLGA, as a most preferred polymer. (Id. at 11: 17-18.)
7. Brodbeck discloses that the lactic acid-based polymer of its
invention has a "number average molecular weight of from about 1,000 to
about 120,000, preferably from about 5,000 to about 30,000 as determined
by gas phase chromatography." (Id. at 11:23-26; see also id. at claim 15.)
5
Appeal2014-006773
Application 11/278,472
8. Brodbeck discloses an especially preferred embodiment where
"the primary solvent is selected from lower alkyl and aralkyl esters of
benzoic acid and the polymer is a lactic-acid based [polymer] preferably
PGLA, having a number average molecular weight of between about 8,000
to about 13,000, preferably about 10,000." (Id. at 13:66-14:4.)
9. Brodbeck discloses that "[t]he low water uptake, i.e., limited
water migration into the gel composition after implantation, permits the
practitioner of the invention to limit beneficial agent transfer by diffusion
and enhance control of the delivery profile of the beneficial agent by
controlling the bioerosion characteristic of the polymer." (Id. at 14:15-20.)
10. Brodbeck discloses that "[t]he limit on the amount of beneficial
agent released in the first 24 hours that is either desired or required will
depend on circumstances such as the overall duration of the delivery
period." (Id. at 16:58---61.) Brodbeck further discloses that, "[t]ypically,
higher percentages of release in the first 24 hours can be tolerated if the
duration of the delivery period is relatively short, e.g., less than 7-14 days."
(Id. at 16:67-17:2.)
11. Brodbeck discloses that, "[ d]epending on the particular solvent
or solvent mixture selected, the polymer and [the] beneficial agent, and
optionally solubility modulators of the beneficial agent," the gel
compositions of its invention may provide different release profile
characteristics such as burst index. (Id. at 17:5-20.)
12. Brodbeck discloses that, "for a given polymer and solvent, by
adjusting the amounts of these components and the amount of the beneficial
agent, one can obtain a release profile that depends more on the degradation
6
Appeal2014-006773
Application 11/278,472
of the polymer than the diffusion of the beneficial agent from the
composition or vice versa." (Id. at 21 :49-54.)
13. Brodbeck discloses that
[r]elease rates and loading of beneficial agent will be adjusted
to provide for therapeutically-effective delivery of the
beneficial agent over the intended sustained delivery period ....
While the release rate ... depends on the particular
circumstances, such as the beneficial agent to be administered,
release rates on the order of from about 0.1 to about 100
micrograms ... for periods of from about 7 to about 90 days
can be obtained. Greater amounts may be delivered if delivery
is to occur over shorter periods.
(Id. at 21:66-22:11.)
Analysis
Claims 11-14, 16, 18-20, 23, and 25-28
We agree with the Examiner that Brodbeck renders claim 11 prima
facie obvious. Brodbeck discloses a method of administering a beneficial
agent to a subject. (FPL) Brodbeck teaches an injectable composition
comprising a bioerodable, biocompatible polymer such as PLGA, a solvent
having miscibility in water of 7% or less selected from esters of benzoic
acid, and a beneficial agent. (FF2, FF6, FF9.) Brodbeck teaches solvent
present in an amount from about 95 to about 20% by weight of the viscous
gel (i.e., the combined amounts of the polymer and the solvent). (FF3.)
Brodbeck teaches that its gel composition can provide controlled release of
the beneficial agent and further discloses various delivery periods including
delivery periods of less than 7-14 days. (FF5, FFlO, FF13.) While
Brodbeck does not explicitly disclose the polymer having a weight average
molecular weight ranging from 3000 to 9000, we find that the Examiner has
7
Appeal2014-006773
Application 11/278,472
made a reasonable showing that the molecular weight of the polymer is a
result effective variable a skilled artisan would look to optimize. "[W]here
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 Aller, 220 F.2d 454, 456 (CCPA 1955).
Appellants contend that Brodbeck does not disclose weight average
molecular weight range of its polymers and only discloses number average
molecular weight. (Appeal Br. 7.) Appellants contend that the number
average molecular weight of a polymer is often much lower than the weight
average molecular weight of the polymer; thus, Appellants argue that "even
if Brodbeck discloses the use of polymers having a number average
molecular weight of about 10,000, such disclosure does not render obvious
the use of polymers having a weight average molecular weight ranging from
3000 to 9000." (Id.)
We are not persuaded. Appellants rely on Brodbeck's disclosure that
the typical polymer molecular weights in the range of 14,400-39,700 weight
average molecular weight translates to 6,400-12,200 number average
molecular weight. (Appeal Br. 7; Brodbeck 25:13-15.) However, Brodbeck
elsewhere discloses that the lactic acid-based polymer of its invention has a
number average molecular weight range between 1,000 to about 120,000.
(FF7.) Even if Appellants were correct that the number average molecular
weight is often much lower than the weight average molecular weight, we
find that it is reasonable to conclude that the lower end of the number
average molecular weight range disclosed in Brodbeck (i.e., 1,000 to
120,000) renders obvious the claimed weight average molecular weight
range of 3,000 to 9,000.
8
Appeal2014-006773
Application 11/278,472
Appellants contend that the Examiner has not shown that the weight
average molecular weight of the polymer is a result effective parameter.
(Appeal Br. 9.) In particular, Appellants argue that,
although Brodbeck generally discloses that the solvent,
polymer, and beneficial agent are variables affecting the burst
index of the composition, Brodbeck fails to disclose what
aspects of the polymer affect burst index. A skilled artisan
would understand that polymers involve many variables other
than molecular weight, including monomer, comonomer,
monomer ratio, end groups. Brodbeck fails to disclose
controlling burst index by adjusting polymer molecular weight,
let alone weight average molecular weight.
(Reply at 7.) We disagree. As Appellants acknowledge, Brodbeck discloses
that, "[ d]epending on the particular solvent or solvent mixture selected, the
polymer and [the] beneficial agent, and optionally solubility modulators of
the beneficial agent," the gel compositions of its invention may provide
different release profile characteristics such as burst index. (FF 11; see also
FF9.) Moreover, molecular weight is an important characteristic of a
polymer, as evidenced by Brodbeck's specification of the range of molecular
weights of the polymers to be used in its invention. (FF7.) We thus find
that the Examiner has established by a preponderance of evidence that
polymer molecular weight is a result effective variable.
We note but find unpersuasive Appellants' contention that it would
not have been obvious to "pick and choose from the broad teachings of
Brodbeck" to arrive at an embodiment having a delivery period of less than
7 days, since such an embodiment is not preferred. (Appeal Br. 9.)
Although Brodbeck defines the term "prolonged period" to mean "a period
of time over which release of a beneficial agent from the implant of the
9
Appeal2014-006773
Application 11/278,472
invention occurs, which will generally be about one week or longer, and
preferably about 30 days or longer" (FF5), Brodbeck clearly suggests that
the release period may be shorter than 7 days and that the release rates may
be adjusted accordingly. (FFlO, FF13.)
Finally, Appellants contend that the claims are non-obvious because
the claimed formulations "surprisingly provide a controlled, sustained
release of beneficial agent over short duration of time." (Appeal Br. 10;
Reply Br. 9-11.) This is not persuasive. As an initial matter, Brodbeck
discloses that its compositions also provide controlled release of beneficial
agents and further suggests that the release period could be shorter than
seven days as claimed. (FF 4, FF 10, FF 13.) Thus, the results set forth in
Appellants' Specification are not unexpected. (Ans. 5.)
Moreover, to the extent Appellants argue that it is surprising that the
claimed low molecular weight polymers provide controlled release over a
short duration of time as compared to polymers with higher molecular
weights outside of the claimed range, the data in the Specification does not
show unexpected results commensurate with the scope of the claims and
does not show the claimed range of molecular weights to be critical. In re
Lindner, 457 F .2d 506, 508 (CCP A 1972) ("It is well established that the
objective evidence of nonobviousness must be commensurate in scope with
the claims.").
In particular, the Specification provides comparative data for only
polymers with molecular weights 7,000 and 8,000, at the higher end of the
claimed range of 3,000 to 9,000. (Specification Tables 1-3.) Neither does
the Specification provide any reasoning why polymers with these two
molecular weights would be representative over the entire claimed range.
10
Appeal2014-006773
Application 11/278,472
Furthermore, the data in the Specification shows that formulation 7-10
contain polymers with molecular weights in the claimed range. 4 (Id. at
Tables 2-3.) However, Figure 6-9 show that none of these formulations
have the claimed release periods of less than seven days, while Figure 9 also
show that formulations 11, containing a polymer with molecular weight
outside of the claimed range, has a release profile similar to formulation 10,
including an apparent release period of approximately nine days. 5
(Specification Table 2-3, Figures 6-9.)
Accordingly, we find claim 11 obvious in light of Brodbeck. Claims
12-14, 16, 18-20, 23, and 25-28 have not been argued separately and
therefore fall with claim 11. 37 C.F.R. § 41.37(c)(l)(iv).
Claims 24, 29, 30-33, 37, and 39
Appellants rely on the same arguments as above in contending that
claims 24, 29, 30-33, 37, and 39 are not obvious. (Appeal Br. 11-15.) We
find these arguments unpersuasive for the same reasons set forth above.
Appellants further contend that the argument for patentability for these
claims is even stronger than for claim 11, because the embodiments used in
the Specification to show unexpected results also fall within these narrower
dependent claims. (Id.) For the reasons already discussed, we are not
persuaded that Appellants have shown evidence of unexpected results that,
4 Formulation 7 contains a polymer with molecular weight of 7,000, and
formulations 8-10 contain polymers with molecular weight of 8,000. (Spec.
Tables 2-3.)
5 Because the last data points in the release profile data in the Specification
do not show a drug plasma level of zero for any of the formulations, it is
unclear whether that data point in fact represents the end of the release
period as Appellants appear to contend. (Appeal Br. 10.) Nevertheless, we
assume that is the case for purposes of this analysis.
11
Appeal2014-006773
Application 11/278,472
when weighed with the evidence supporting the prima facie case, show these
claims to be non-obvious. We thus find these claims obvious in light of
Brodbeck as well.
SUMMARY
For the reasons above, we affirm the Examiner's decision rejecting
claims 11-14, 16, 18-20, 23-33, 37, and 39.
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
12