Ex Parte Bosch et al

Board of Patent Appeals and Interferences

Jan 10, 2011

10619539 (B.P.A.I. Jan. 10, 2011)

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.
10/619,539 07/16/2003 H. William Bosch 029318-0961 6324
31049 7590 01/10/2011
Elan Drug Delivery, Inc. c/o Foley & Lardner
3000 K Street, N.W.
Suite 500
Washington, DC 20007-5109
EXAMINER
TRAN, SUSAN T
ART UNIT PAPER NUMBER
1615
MAIL DATE DELIVERY MODE
01/10/2011 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 BOARD OF PATENT APPEALS
AND INTERFERENCES
____________

Ex parte WILLIAM H. BOSCH, MATTHEW R. HILBORN, DOUGLAS C.
HOVEY, LAURA J. KLINE, ROBERT W. LEE, JOHN D. PRUITT,
NIELS P. RYDE, TUULA A. RYDE, and SHUQIAN XU
____________

Appeal 2010-011060
Application 10/619,539
Technology Center 1600
____________

Before RICHARD TORCZON, ROMULO H. DELMENDO, and
RICHARD M. LEBOVITZ, Administrative Patent Judges.

LEBOVITZ, Administrative Patent Judge.

DECISION ON APPEAL1

1 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, or for filing a request for rehearing,
as recited in 37 C.F.R. § 41.52 begins to run from the “MAIL DATE” (paper
delivery mode) or the “NOTIFICATION DATE” (electronic delivery mode)
shown on the PTOL-90A cover letter attached to this decision.
Appeal 2010-011060
Application 10/619,539

2
This is a decision on the appeal under 35 U.S.C. § 134 by the Patent
Applicants from the Patent Examiner’s rejections of claims 1-3, 5-35, 37, 39,
41, and 43-45. The Board’s jurisdiction for this appeal is under 35 U.S.C.
§§ 6(b). We affirm.

STATEMENT OF THE CASE
The claims are directed to stable nanoparticulate liquid dosage
compositions. According to the Specification, nanoparticulate liquid dosage
compositions can be prone to crystal growth (Spec. 4:29-30). The
Specification states:
the invention is directed to the surprising discovery that
commonly used, non-toxic pharmaceutical ingredients which
are osmotically active, such as glycerol, mannitol, and sodium
chloride, can function as crystal growth inhibitors in liquid
dosage compositions of nanoparticulate active agent.
(Spec. 8:5-9.)
The pending claims stand rejected by the Examiner as follows:
1. Claims 1-3, 5, 6, 8-19, 21-24, 27-29, 32-35, 37, 39, 41, and 43-45
under 35 U.S.C. § 102(b) as anticipated by Liversidge ‘4012 (Answer 5);
2. Claims 1-3, 5-24, 26-31, 35, 37, 39, 41, and 43-45 under 35 U.S.C.
§ 102(e) as anticipated by Kipp ‘3293 (id. at 7);
3. Claims 1-3, 5-24, 27-29, 32-35, 37, 39, 41, and 43-45 under 35
U.S.C. § 103 as obvious over Liversidge ‘041 in view of Brockbank4 or
Kipp ‘329 (id. at 8);

2 Method to Reduce Particle Size Growth During Lyophilization, U.S. Patent
No. 5,302,401 (filed Dec. 9, 1992) (issued Apr. 12, 1994).
3 Compositions of and Method for Preparing Stable Particles in a Frozen
Aqueous Matrix, U.S. Patent Application No. 2003/0077329 (filed Oct. 11,
2002) (published Apr. 24, 2003).
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4. Claims 25-35, 37, 39, 41, and 43-45 under 35 U.S.C. § 103 as
obvious over Liversidge ‘041 and Liversidge ‘0495 (id. at 9);
5. Claim 2 under 35 U.S.C. § 112, ¶ 1, as failing to comply with the
enablement requirement (id. at 4); and
6. Claim 15 under 35 U.S.C. § 112, ¶ 2, as indefinite (id. at 4-5).
Claim 1 is representative and reads as follows:

1. A stable nanoparticulate liquid dosage composition
comprising:
(a) particles of at least one active agent having an
effective average particle size of less than 2000 nm;
(b) at least one surface stabilizer;
(c) at least one osmotically active crystal growth inhibitor
that is capable of preventing crystal growth of the active agent
at ambient temperature, wherein the osmotically active crystal
growth inhibitor is selected from the group consisting of
glycerol, propylene glycol, mannitol, sucrose, glucose, fructose,
mannose, lactose, xylitol, sorbitol, trehalose, a
polysaccharide, a mono-polysaccharide, a di-polysaccharides
[sic], a sugars [sic], a sugar alcohol, sodium chloride, potassium
chloride, magnesium chloride, and an ionic salt; and
(d) a liquid media [sic],
wherein the liquid dosage composition does not
incorporate a cloud point modifier.

FINDINGS OF FACT (FF)
Liversidge ‘401
1. Liversidge ‘401 describes a composition comprising:

4 Cyclohexanediol Cryoprotectant Compounds, International Publication No.
WO 01/78505 (filed Apr. 17, 2001) (published Oct. 25, 2001).
5 Novel Griseofulvin Compositions, U.S. Patent Application No.
2005/0004049 (filed Oct. 14, 2003) (published Jan.6, 2005).
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2. nanoparticles containing a poorly soluble therapeutic or diagnostic agent
(col. 1, ll. 53-54 & col. 2, ll. 1-5);
3. a surface modifier adsorbed on the surface the nanoparticles (col. 1, ll.
53-55);
4. a cryoprotectant (col. 1, ll. 55-56); and
5. a liquid medium (col. 5, ll. 43-44 & 52-53).
6. The average particles size is less than about 400 nm (col. 4, l. to col. 5, l.
14).
7. Liversidge ‘401 teaches that conventional lyophilization leads to
agglomeration and growth in nanoparticle size, but the “invention describes
the application of lyophilization to preparation of freeze-dried drug
nanoparticles that retain their small particle size” and with “reduced or no
particle size growth” (col. 1, ll. 19-30).
8. Liversidge ‘401 teaches:
Cryoprotectants (cryoprotective agents or compounds) are
agents that protect chemical compounds, cells, or tissues from
the deleterious effects of freezing that may accompany
lyophilization. In the case of nanoparticles, cryoprotectants
protect from the agglomeration caused by the process of
lyophilization, namely freeze-drying.
(Col. 5, ll. 20-26)
9. Liversidge ‘401 lists exemplary cryoprotectants, such as sucrose,
mannitol, surface active agents such as the Tweens, and glycerol (col. 5, l.
27-33) and uses sucrose, mannitol, and Tween 80 in its examples (col. 6-col.
7).
10. In the examples, Liversidge ‘401 reported that Tween 80 or 2%
mannitol in the original dispersion did not significantly decrease the large
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particle size after reconstitution, but addition of 2% sucrose to the initial
dispersion led reduced particle size during lyophilization.

Kipp ‘329
11. Kipp ‘329 describes a composition of a stable nanoparticle suspension
of a poorly water soluble pharmaceutical agent suspended in a “frozen
aqueous matrix” where the “freezing may circumvent” instability problems
(Abstract; ¶¶ 39-40).
12. Kipp ‘329 describes methods of making nanoparticle suspensions in an
aqueous matrix (¶ 46).
13. Kipp ‘329 teaches that its composition can comprise:
14. • surface modifiers (¶ 42);
15. • cryoprotectants (id.);
16. • osmotic agents (id.); and
17. • crystal growth modifiers (id.).
18. The nanoparticles are described as preferably less than about 2 µm, and
even more preferably less 200 nm (¶ 78).
19. Cryoprotectants include sucrose, mannitol, glycerol, and Tweens (¶ 71).
20. Osmotic agents include mannitol, glycerol, and sodium chloride (¶ 73).

LEGAL PRINCIPLES
“To anticipate a claim, a prior art reference must disclose every
limitation of the claimed invention, either explicitly or inherently.” In re
Schreiber, 128 F.3d 1473, 1477 (Fed. Cir. 1997).
In some cases, the inherent property corresponds to a claimed
new benefit or characteristic of an invention otherwise in the
prior art. In those cases, the new realization alone does not
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render the old invention patentable. See Atlas Powder, 190 F.3d
at 1347 (“[T]he discovery of a previously unappreciated
property of a prior art composition, or of a scientific
explanation for the prior art’s function, does not render the old
composition patentably new to the discoverer.”).
Perricone v. Medicis Pharm. Corp., 432 F.3d 1368, 1377 (Fed. Cir. 2005).
“[W]hen the PTO shows sound basis for believing that the products of
the applicant and the prior art are the same, the applicant has the burden of
showing that they are not.” In re Spada, 911 F.2d 705, 708 (Fed. Cir. 1990).

ANTICIPATION BY LIVERSIDGE
Issue
The Examiner found that all four components a) through d) of claim 1
are described in Liversidge ‘401, anticipating the claimed composition
(Answer 5-6; FF1-FF6). Appellants contend that the Examiner erred in
finding that Liversidge ‘401 described the claimed subject matter.

Lyophilized composition
Appellants contend that Liversidge ‘401 describes a lyophilized
composition, not a liquid composition as recited in claim 1 (App. Br. 9).
Appellants contend that “the mixture of a suspension of drug nanoparticles
and a solution of cryoprotectant is only an intermediate product rather than a
final product” which is further processed by lyophilization (Reply Br. 8-9).
Liversidge ‘401 expressly described an aqueous composition (FF5). It
is not removed from the prior art simply because it is an “intermediate”
which is subsequently subjected to lyophilization. In re Mullen, 481 F.2d
1333, 1336 (CCPA 1973) (“the intermediate structure of Haigis was both
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intended and appreciated. It matters not one whit that it was intended to be
and appreciated as being an intermediate structure rather than an end use
item.”)

All elements not as arranged in the claim
Appellants contend “it is insufficient to support an anticipation
rejection by merely pointing out certain claim elements in the cited
reference. The Examiner is required to articulate how the elements are
‘arranged as in the claim.’” (Reply Br. 9.)
Claim 1 is directed to composition comprising four components. The
Examiner explained on pages 5-6 and 10 of the Answer how Liversidge ‘401
described all the components of claim 1 (FF1-FF6). Appellants did not
identify an error in the Examiner’s findings, and upon review, we find no
defect in them.

Cryoprotectant of Liversidge ‘401 does not teach or suggest claimed crystal
growth inhibitor
Appellants contend that Liversidge 401’s description of a
cryoprotectant does not teach or suggest the claimed crystal growth
inhibitor. First, Appellants contend that cryoprotectants have a different
function than crystal growth inhibitors (Reply Br. 10). Appellants state that
crystal growth inhibitors prevent an increase in crystal size at ambient
temperature, while cryoprotectants function during the freezing and
lyophilization process (Reply Br. 10; FF7 & FF8). Consequently, they
contend the ordinary skilled worker would not have been “led” by
Liversidge ‘401 to pick a crystal growth inhibitor (Reply Br. 10). Second,
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Appellants contend that Liversidge ‘401 lists mannitol and Tween as
cryoprotectants, but Liversidge’s shows that mannitol and Tween were not
suitable in its working examples (id. at 11).
To be clear, the Examiner found that Liversidge ‘401’s composition,
prior to lyophilization, anticipated the claimed subject matter (Answer 5-6).
This composition comprises cryoprotectants – including mannitol, a
compound which is specifically claimed (claim 6) and used in certain
examples described in Liversidge ‘401 (FF9 & FF10). While Liversidge
‘401 may not have appreciated that mannitol, or the other identified
cryoprotectants, had additional properties in preventing crystal growth at
ambient temperature, recognition of an inherent property is not a basis for
patentability. Perricone, 432 F.3d at 1377.
Appellants’ argument about being “led” to choose a crystal growth
inhibitor is not persuasive because the rejection is based on anticipation, not
obviousness. The Examiner’s position is that Liversidge ‘401 described the
claimed composition. The Examiner provided evidence that several of
Liversidge 401’s cryoprotectants were the same as the claimed crystal
growth inhibitors, shifting the burden to Appellants to show otherwise. In re
Best, 562 F.2d 1252, 1255 (CCPA 1977). While Appellants argue the two
classes of agents are not equivalent functionally, insufficient evidence has
been provided that Liversidge ‘401’s cryoprotectants would not inherently
serve as crystal growth inhibitors.
Appellants point out that mannitol and Tween did not prevent crystal
growth in certain examples described by Liversidge ‘401 (FF10; Reply Br.
11). Again, we note that the basis of the rejection is anticipation. The
efficacy of these compounds in reducing particle size growth does not alter
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the fact that the prior art liquid composition of Liversidge ‘401, prior to
lyophilization, comprised all four components of the claimed composition.

Stability
Appellants contend that the “stable” limitation of claim 1 is not met
(Reply Br. 9 & 12).
Based on the identity between the claimed components, the
nanoparticle sizes, and Liversidge 401’s comparable composition (FF6 &
FF7), the Examiner had a reasonable basis for believing that Liversidge ‘401
met all the limitations of the claim. Appellants contend that Liversidge
401’s composition is not “stable,” and define stable as having a particle size
of less than 2000 nm (Reply Br. 12), but they have not shown error in the
Examiner’s finding that Liversidge 401’s liquid composition, prior to
lyophilization, met this particle size limitation (FF6).

Summary
We affirm the rejection of claim 1. Claims 2, 3, 5, 6, 8-19, 21-24, 27-
29, 32-35, 37, 39, 41, and 43-45 were not separated argued, and therefore
fall with claim 1. 37 C.F.R. § 41.37(c)(1)(vii).

ANTICIPATION BY KIPP ‘329
Issue
The Examiner found that Kipp ‘329 described all four components of
the claimed liquid dosage composition. Appellants contend that the
Examiner erred in this determination.

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Kipp ‘329 is a frozen composition
Appellants contend that Kipp ‘329 describes a “frozen aqueous
matrix,” not a liquid dosage form as in claim 1 (App. Br. 10).
This argument fails to acknowledge the plain fact that Kipp ‘329
describes a liquid composition prior to freezing (FF11 & FF12).
Consequently, we accord this argument no weight.

Kipp ‘329 does not teach crystal growth inhibitors
Appellants contend it “is unclear which compound the Examiner
deems to teach the osmotically active crystal growth inhibitor of the claimed
invention because the Examiner simply cites to paragraph[s] . . . , absent any
elaboration on how any of these compounds teaches the claimed crystal
growth inhibitor.” (Reply Br. 13).
We do not agree. The Examiner identified mannitol as one of Kipp
‘329’s osmotic agents (Answer 7; FF20), which is specifically claimed by
Appellants as a crystal growth inhibitor (claim 6). The Examiner also
pointed to paragraph 71 of Kipp ‘329 for teaching cryoprotectants (Answer
7). Mannitol is also specifically listed in paragraph 71 (FF19). Thus, it was
quite clear from the Examiner’s Answer that either Kipp’s osmotic agents or
cryoprotectants were considered by the Examiner as anticipating the claimed
class of crystal growth inhibitors.
Mannitol is described by Kipp ‘329 (FF19 & FF20) and characterized
in the Specification as a crystal growth inhibitor (Spec. 8:5-9). Appellants’
assertion that “Kipp fails to expressly disclose any of the crystal growth
modifiers required by the present claims” is therefore not true. (Reply Br.
14).
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Summary
We affirm the rejection of claim 1. Claims 2, 3, 5-24, 26-31, 35, 37,
39, 41, and 43-45 were not separated argued, and therefore fall with claim 1.
37 C.F.R. § 41.37(c)(1)(vii).

OBVIOUSNESS OVER LIVERSIDGE ‘401 IN VIEW OF
BROCKBANK OR KIPP ‘329
We adopt the Examiner’s fact-finding and reasoning as set forth in the
Answer (pp. 8-9). Appellants contend that Liversidge ‘401 and Kipp ‘329
were improperly combined because each take different approaches in
creating stable nanoparticle compositions (App. Br. 10-11). The Examiner
properly responded to this argument by pointing out that Brockbank and
Kipp ‘329 were cited for their teaching that sodium chloride is a
cryoprotectant (Answer 13). Because a compound and its properties are
inseparable, a person of ordinary skill in the art would have had a reasonable
expectation that sodium chloride would retain its inherent function as a
cryoprotectant in Liversidge ‘401 as well. Appellants did not show
otherwise.
We affirm the rejection of claims 1-3, 5-24, 27-29, 32-35, 37, 39, 41,
and 43-45.

OBVIOUSNESS OVER LIVERSIDGE ‘401 AND LIVERSIDGE ‘049
Appellants acknowledge that the rejected dependent claims 25-35, 37,
39, 41, and 43-45 stand or fall together with the rejected base claims (App.
Br. 11). As we affirmed the rejection of the base claims, we affirm this
rejection as well for the reasons stated by the Examiner.
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SECTION 112 REJECTIONS
Appellants did not challenge the propriety of the grounds of rejection
under Section 112 (Rejections 5 & 6). Rather, Appellants contend certain
procedural actions by the Examiner denied them the “fair opportunity to
submit claim amendments” (App. Br. 8).
The Board’s jurisdiction is over decisions by a primary examiner to
reject claims. 35 U.S.C. § 134(a). Consequently, whether the procedure
followed by Examiner was proper is not a matter for us to decide. We
affirm the rejections of the claims under Section 112 for the reasons given
by the Examiner.

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

KMF

Elan Drug Delivery, Inc.
c/o Foley & Lardner
3000 K Street, N.W.
Suite 500
Washington DC 20007-5109