Ex Parte Bosch et al

Board of Patent Appeals and Interferences

Apr 26, 2010

10851661 (B.P.A.I. Apr. 26, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
____________________

Ex parte H. WILLIAM BOSCH
and JANINE KELLER
____________________

Appeal 2009-010928
Application 10/851,661
Technology Center 1700
____________________

Decided: April 26, 2010
____________________

Before MICHAEL P. COLAIANNI, LINDA M. GAUDETTE, and
KAREN M. HASTINGS, Administrative Patent Judges.

COLAIANNI, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on an appeal under 35 U.S.C. § 134 from the
Examiner's final rejection of claims 22 through 42. Claims 1 through 21
and 43, the other claims pending in this application, stand withdrawn from
consideration by the Examiner. We have jurisdiction pursuant to 35 U.S.C.
§ 6.
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We AFFIRM.
STATEMENT OF THE CASE
The subject matter on appeal is directed to a composition. Claim 22
is illustrative:
22. A composition comprising a dispersion of one or more
nanoparticulate active agents comprising:

(a) an aqueous liquid dispersion media;

(b) at least one active agent which is poorly soluble in
the liquid dispersion media and which has an effective average
particle size of less than about 1 micron, and

(c) at least one surface stabilizer associated with the
surface of the active agent;

wherein the dispersion has been sterilized by subjecting
the dispersion to gamma irradiation.

As evidence of unpatentability of the claimed subject matter, the
Examiner relies upon the following references:
Unger 6,123,923 Sep. 26, 2000
Bosch 6,428,814 B1 Aug. 6, 2002
Bernini 6,464,958 B1 Oct. 15, 2002
Kipp US 2003/0077329 A1 Apr. 24, 2003
Wertz US 2003/0185869 A1 Oct. 2, 2003
Britten US 2003/0219461 A1 Nov. 27, 2003

As evidence of patentability of the claimed subject matter, Appellants
rely upon the following references:
Sintzel et al., "Influence of irradiation sterilization on a semi-solid
poly(ortho ester)," Int. J. Pharma. 175, 165-176 (1988) (hereinafter
"Sintzel").
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Seino et al., "Hydrogen evolution from water dispersing nanoparticles
irradiated with gamma-ray/Size effect and dose rate effect, Scripta
Materialia 44, 1709-1712 (2001) (hereinafter "Seino").

Faisant et al., "The effect of gamma-irradiation on drug release from
bioerodible microparticles: a quantitative treatment," Int. J. Pharma. 242,
281-284 (2002) (hereinafter "Faisant").

The Examiner maintains the following rejections:
1) Claims 22-30, 33-37, 41, and 42 under 35 U.S.C. 103(a) as
unpatentable over Bosch, Kipp, and Bernini;
2) Claims 31 and 32 under 35 U.S.C. 103(a) as unpatentable over
Bosch, Kipp, and Bernini, and further in view of Wertz; and
3) Claims 38-40 under 35 U.S.C. 103(a) as unpatentable over Bosch,
Kipp, and Bernini, and further in view of Britten or Unger1.
With respect to rejection (1), we address the rejection with respect to
claim 22 only as argued by Appellants. See 37 C.F.R. § 41.37(c)(1)(vii).
With respect to rejections (2) and (3), Appellants provide no additional
argument for these rejections and instead refer to the arguments made
regarding claim 22 in rejection (1). (App. Br. 17-20). Therefore, rejections
(2) and (3) stand or fall with our decision regarding the rejection of claim 22
in rejection (1).

1 We note Appellants' inadvertent omission of Kipp in Rejections (2) and (3)
at page 8 of the Appeal Brief is harmless error since it is apparent from
pages 8-10 of the Answer that this reference is included in the rejections.
Accordingly, we include the correct statement of the rejections as
understood by the Examiner and Appellants.

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ISSUE
Did the Examiner reversibly err in determining that the sterile
dispersion suggested by Bosch in view of Kipp and Bernini meets the
sterilized dispersion feature required by claim 22? We decide this issue in
the negative.

FINDING OF FACT
1. Bosch teaches that "[c]ompositions suitable for parenteral injection
may comprise physiologically acceptable sterile aqueous or
nonaqueous dispersions, suspensions or emulsions." (Bosch, col. 21,
ll. 25-29) (emphasis added).

PRINCIPLE OF LAW
“The patentability of a product does not depend on its method of
production. If the product in a product-by-process claim is the same as or
obvious from a product of the prior art, the claim is unpatentable even
though the prior product was made by a different process.” In re Thorpe,
777 F.2d 695, 697 (Fed. Cir. 1985) (citations omitted).
As stated in In re Best,

Where . . . the claimed and prior art products are identical
or substantially identical, or are produced by identical or
substantially identical processes, the PTO can require an
applicant to prove that the prior art products do not necessarily
or inherently possess the characteristics of his claimed product.
Whether the rejection is based on ‘inherency’ under 35 U.S.C.
§ 102, on ‘prima facie obviousness' under 35 U.S.C. § 103,
jointly or alternatively, the burden of proof is the same, and its
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fairness is evidenced by the PTO's inability to manufacture
products or to obtain and compare prior art products.

562 F.2d 1252, 1255 (CCPA 1977) (citations omitted).
"[A]n applicant relying on comparative tests to rebut a prima facie
case of obviousness must compare his claimed invention to the closest prior
art." See In re De Blauwe, 736 F.2d 699, 705 (Fed. Cir. 1984).

ANALYSIS AND CONCLUSION
We begin by noting that the sterilized dispersion feature required by
claim 22 is claimed in a product-by-process format such that the product is
the focus of our inquiry and not its method of production. See Thorpe, 777
F.2d at 697.
Turning our attention to the rejection, Appellants argue that
[a]t page 11 of the Answer, the Examiner states that "it
should be noted that the dispersions of Bosch are used in
Prescription drugs and are therefore inherently sterile." This
assertion . . . is unsupported by any evidence or citation
provided by the Examiner.
Moreover, the statement is incorrect. The mere fact that a
composition is intended for pharmaceutical use does not imply
that it is sterile. . . . A person of ordinary skill would draw no
conclusion regarding [the] sterility of a composition unless it
was expressly stated in the reference.

(Reply Br. 6-7).
While the Examiner states at page 11 of the Answer that "dispersions
of Bosch are used in Prescription drugs and are . . . inherently sterile”, the
Examiner’s rejection is not based solely on this finding. Rather, the
Examiner further explains that “since this is a composition claim; the
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method of sterilization would not appear to impact the final product." (Ans.
11).
Indeed, Bosch teaches that "[c]ompositions suitable for . . . injection
may comprise . . . sterile aqueous . . . dispersions." (FF 1). Thus, because
Bosch explicitly teaches a sterile aqueous dispersion, we agree with the
Examiner’s finding that Bosch’s aqueous dispersion is inherently sterile and
satisfies the sterilized dispersion product-by-process feature of claim 22.
In addition, because the Examiner found that Bosch's sterile aqueous
dispersion is virtually identical to Appellants’ sterilized dispersion, the
burden was properly shifted to Appellants to prove that a dispersion
sterilized by gamma irradiation (claim 22) is patentably different from
Bosch’s sterile aqueous dispersion. See Thorpe, 777 F.2d at 697 and Best,
562 F.2d at 1255.
Attempting to meet this burden, Appellants rely on portions of their
Specification as evidence of unexpected results and argue that the
"[s]terilization of the claimed dispersion by gamma radiation imparts a[n
unexpected] structural distinctiveness to the claimed dispersion." (Reply Br.
9-10). Specifically, Appellants argue that 1) "[the] particle size[s] of
radiation-sterilized aqueous nanoparticulate active agent [in a] dispersion are
more stable than those not treated by radiation;" 2) "gamma irradiat[ion]
[of] an aqueous dispersion of an active agent . . . [may be done] without
significant degradation of the active agent;" and 3) "degradation products
are detectible in the gamma irradiation samples that are not found in non-
irradiated samples." (Reply Br. 9).
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As noted by the Examiner, Appellants’ results cannot be unexpected
because such results are disclosed by Bernini (Ans. 12). In other words,
Appellants have not compared their claimed invention to the closest prior art
(e.g., Bosch or Bernini). See De Blauwe, 736 F.2d at 705. In this regard,
Appellants compare their claimed invention with a "control sample (no
radiation exposure)" (See Spec. 30). Appellants, however, do not allege or
direct us to any credible evidence showing that this "control sample (no
radiation exposure)" has been sterilized.
Indeed, Appellants provide no test data showing that the dispersion
taught by the closest prior art (e.g., Bosch or Bernini) does not have this
unexpected "structural distinctiveness."
In other words, Appellants have not explained how their dispersion
sterilized via gamma irradiation is patentably different from Bosch’s
sterilized aqueous dispersion or Bernini's sterile suspension.
For example, the exemplified embodiments of Bernini relied upon by
the Examiner at pages 11 and 12 of the Answer, teach that gamma irradiated
particles are stably suspended in an aqueous solution like Appellants’
claimed composition. (See also Bernini, col. 7, ll. 24-61 and col. 8, ll. 28-
30).
Thus, given the above, Appellants have not established that the
claimed dispersion is patentably different from the dispersion suggested by
Bosch in view of Kipp and Bernini.
Appellants also argue that the Examiner has failed to establish a prima
facie case of obviousness because “no reason, no suggestion why, and no
implication was proffered as to why one of ordinary skill in the art would
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look to the three cited references, parse out each individual element, and
combine them as recited in claim 22.” (App. Br. 10).
Appellants also argue that
[f]urthermore . . . [p]roducts may be made sterile, for
example, by exposure to radiation (including γ or β), electron-
beams, dry heat, moist heat (i.e., autoclaved), chemical
treatment (e.g. ethylene oxide, formaldehyde), filtration through
a .22 micron filter, or aseptic combination when the starting
materials have been pre-sterilized. Each known sterilization
technique has drawbacks and advantages. Thus, even though
gamma radiation was known to be suitable for dry compositions
(e.g., as disclosed by Bernini), it was thought that gamma
irradiation was inappropriate for aqueous dispersions because
the presence of water would cause degradation of the active
agent.

(Reply Br. 7). Also, Appellants argue that Bernini teaches away from the
claimed invention because Bernini is "limited to the sterilization of solid
powders." (App. Br. 12). Appellants also argue that Kipp teaches away
from the combination of claimed elements because Kipp teaches "preparing
stable particles in a frozen aqueous matrix." (App. Br. 14).
In addition, Appellants cite to Seino, Sintzel, and Faisant as evidence
to support their argument that a “person of ordinary skill in the art at the
time the claimed invention was made would not have considered gamma
irradiation suitable for sterilization of an aqueous dispersion of an active
agent.” (App. Br. 13).
All of these arguments and evidence, however, fail to address and thus
fail to refute the Examiner’s determinations that Bosch discloses that its
dispersion is inherently sterile and that regardless of the method used to
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obtain a sterile dispersion, the sterile dispersion of Bosch in view of Kipp
and Bernini meets the sterilized dispersion feature required by claim 22.
For example, Appellants' arguments that different processes of
making a sterile dispersion have "drawbacks and advantages" focus on
different sterilization processes and not on the sterile aqueous dispersion
suggested by Bosch in view of Kipp and Bernini.
As noted above, Appellants have not established that the claimed
gamma irradiated aqueous dispersion patentably differs from the sterile
dispersion suggested by Bosch in view of Kipp2 and Bernini.
Thus, Appellants have not persuaded us that the Examiner reversibly
erred in determining that the sterile dispersion suggested by Bosch in view
of Kipp and Bernini meets the sterilized dispersion feature required by claim
22.

ORDER
The Examiner's § 103 rejection is sustained. Accordingly, the
decision of the Examiner is affirmed.

TIME PERIOD
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1) (2009).

AFFIRMED

2 We note that Kipp is cumulative to the teachings of Bosch.
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ELAN DRUG DELIVERY, INC.
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