Ex Parte Muller et al

Board of Patent Appeals and Interferences

Jan 13, 2012

10030417 (B.P.A.I. Jan. 13, 2012)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte RAINER H. MULLER, KARSTEN KRAUSE,
and KARSTEN MADER
__________

Appeal 2011-007441
Application 10/030,417
Technology Center 1600
__________

Before DONALD E. ADAMS, ERIC GRIMES, and LORA M. GREEN,
Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims relating to
superfine micro- and nanoparticles. The Examiner has rejected the claims as
obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm-in-part.
STATEMENT OF THE CASE
Claims 1-17, 20, 24-29, 31-34, and 38-47 are on appeal. Claims 1 and
27 are representative and read as follows:
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1. Process for the gentle preparation of superfine micro and
nanoparticles having a particle size, as average diameter of the number
distribution, of 5.6 μm or less, the method comprising:
subjecting a matrix material comprising solid particles to a high
pressure homogenizing process in a piston-gap homogenizer in an anhydrous
or water-reduced dispersion medium containing less than 50 wt.% of water
in which the solid particles are suspended and at temperatures of 20°C or
less, which leads to a gentle particle size reduction with minimization of the
impairment of the chemical stability of the homogenized material, to form
superfine micro- and nanoparticles.

27. Superfine micro- or nanoparticle dispersions having a particle
size, as average diameter of the number distribution, of 5.6 μm or less,
prepared according to a process comprising:
subjecting a matrix material to a high-pressure homogenizing process
in a piston-gap homogenizer in an anhydrous or water-reduced medium
containing less than 50 wt.% of water and/or at low temperatures of 20°C or
less, which leads to a gentle particle size reduction with minimization of the
impairment of the chemical stability of the homogenized material and forms
a dispersion comprising the superfine micro- or nanoparticles.

The Examiner has rejected claims all of the claims on appeal under 35
U.S.C. § 103(a) as being obvious in view of Desai1 and Muller.2 The
Examiner finds that Desai discloses the “preparation of microparticles or
nanoparticles of water insoluble drugs,” where the particles are less than 200
nm in size (Answer 3). The Examiner finds that Desai discloses that the
“drug is dissolved in an organic solvent…, a protein such as albumin is
added to stabilize the nanoparticles … and the mixture is homogenized
under high-pressure homogenization” (id.). The Examiner finds that Desai

1 Desai et al., WO 98/14174, Apr. 9 1998
2 Muller et al., US 5,858,410, Jan. 12, 1999
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discloses a “water-reduced dispersion medium … wherein the taxol is
dispersed in ethanol which is free of water” (id. at 4).
The Examiner finds that Desai does not teach a piston-gap
homogenizer, but Muller discloses “nanoparticles of drugs … made by
dispersing solid therapeutically active drugs in a solvent and subjecting the
dispersion to high-pressure homogenization in a piston-gap homogenizer …
at room temperature” (id.). The Examiner concludes that “it would have
been obvious to one of ordinary skill in the art to make paclitaxel
nanoparticles according to the methods disclosed by Desai and homogenize
it in a piston-gap homogenizer because Muller teaches that … by conversion
of the microparticles into nanoparticles by means of a high-energy process
… solubility increases greatly” (id. at 5).
Appellants contend that the process of claim 1 requires piston-gap
homogenization “in an anhydrous or water-reduced dispersion medium
containing less than 50 wt.% of water” and “both Muller and Desai require
the use of water in amounts greater than the claimed less than 50 wt.% as the
dispersion medium” (Appeal Br. 5).
We agree with Appellants that the Examiner has not adequately
shown that the cited references would have made obvious the process claims
on appeal. Desai discloses methods for the preparation of water insoluble
pharmacologically active agents which comprise
subjecting a mixture comprising: an organic phase containing
said pharmacologically active agent dispersed therein, and
aqueous medium containing biocompatible polymer wherein
said mixture contains substantially no surfactants, in a high
pressure homogenizer at a pressure in the range of about 3,000
up to 30,000 psi.
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(Desai 14: 10-21.)
All of Desai’s working examples include homogenization of
compositions comprising greater than 50% water (id. at 33-42). Although
the Examiner cites Desai’s Example 4 as disclosing a dispersion with
reduced water or no water (Answer 6), that example actually states: “30 mg
Taxol is dissolved in 0.55 ml chloroform and 0.05 ml ethanol. The solution
is added to 29.4 ml of Tween 80 solution (1% w/v) , which is presaturated
with 1% chloroform. The mixture is homogenized.” (Id. at 35: 21-24.) A
1% Tween 80 solution that includes 1% chloroform is 98% water and thus,
Desai’s Example 4 describes homogenization of a composition that contains
greater than 50% water.
The Examiner also argues that “Muller teaches literally that ‘since the
lowest possible surfactant content is desirable … surfactant-free
nanosuspensions have also been prepared’ (col. 8, lines 27+)” (Answer 6).
We do not agree that this disclosure describes the water-reduced medium
required by the process claims on appeal.
Muller discloses “a drug carrier comprising particles of at least one
pure active compound which is insoluble, … sparingly soluble or moderately
soluble in water, aqueous media and/or organic solvents” (Muller, abstract).
Muller discloses that “[s]uspensions were prepared with a drug, which was
ground in an air jet, in an aqueous surfactant solution.… The suspension was
homogenized in a piston-gap homogenizer.” (Id. at col. 5, ll. 27-31.) All of
Muller’s examples describe compositions for homogenization that contain
greater than 50% water (id. at cols. 11-18). The Examiner cites Muller’s
reference to its Example 13 as showing surfactant-free compositions, but
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that example describes a surfactant-free composition that nevertheless
contains greater than 50% water.
Thus, neither Desai nor Muller discloses or suggests the
homogenization of compositions containing less than 50 wt.% water, and the
Examiner has not adequately explained why that limitation would have been
obvious to one of ordinary skill in the art. The rejection of independent
claim 1, and dependent claims 2-17, 20, 24-26, 28, 29, 31-34, and 38-44 is
reversed.
Independent claims 46 and 47 are also directed to processes that
include dispersing solid particles “in an anhydrous or water-reduced
dispersion medium containing less than 50 wt.% of water form a pre-
suspension; and subjecting the pre-suspension to a high-pressure
homogenizing process in a piston-gap homogenizer to reduce the particle
size.” Thus, the rejection of claims 46 and 47 is also reversed for the
reasons discussed above.
The Examiner has also rejected independent claim 27 as being
obvious in view of Desai and Muller, based on the disclosures discussed
above. Claim 27 is directed to a product that is defined, in part, by the
method by which it is made.
Appellants argue that claim 27 is not obvious over Desai and Muller
for the same reasons discussed above for the process claims (Appeal Br. 12).
Appellants also argue that “[s]ince the claimed particles are produced using
the gentle homogenization, without the high shock waves of cavitation, less
damage to the homogenized material is present compared to the particles
produced using cavitation according to Muller” (id.).
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Appellants’ arguments are not persuasive. Claim 27 recites “high-
pressure homogenizing process in a piston-gap homogenizer in an anhydrous
or water-reduced medium containing less than 50 wt.% of water and/or at
low temperatures of 20°C or less” (claim 27, emphasis added). The claim
thus reads on carrying out the homogenization either in a water-reduced
medium or at a temperature of 20°C or less. Since Muller discloses
nanoparticle dispersions having an average particle size of 10 nm to 1,000
nm that were prepared by subjecting a powdered drug compound (i.e., a
matrix material) to high-pressure homogenization in a piston-gap
homogenizer at room temperature, which would reasonably include 20°C or
less, we conclude that claim 27 is anticipated by Muller. Thus, we affirm
the rejection of claim 27 as being obvious in view of Desai and Muller since
“[i]t is well settled that ‘anticipation is the epitome of obviousness.’” In re
McDaniel, 293 F.3d 1379, 1385 (Fed. Cir. 2002). Claim 45 falls with claim
27 (Appeal Br. 5, 12; 37 C.F.R. § 41.37(c)(1)(vii)).
SUMMARY
We reverse the rejection of claims 1-17, 20, 24-29, 31-34, and 38-47
under 35 U.S.C. § 103(a). However, we affirm the rejection of claims 27
and 45 under 35 U.S.C. § 103(a).

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Application 10/030,417

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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-IN-PART

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