Ex Parte Richard

Patent Trial and Appeal Board

Sep 25, 2012

11856237 (P.T.A.B. Sep. 25, 2012)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte ROBERT E. RICHARD
__________

Appeal 2011-005836
Application 11/856,237
Technology Center 1600
__________

Before TONI R. SCHEINER, ERIC GRIMES, and JEFFREY N. FREDMAN,
Administrative Patent Judges.

SCHEINER, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 from the final rejection of
claims 1, 3-5, 7-11, 13-15, 31, 45, 48, 49, and 52, directed to a polymeric
particle. The claims have been rejected as obvious. We have jurisdiction
under 35 U.S.C. § 6(b).
We affirm-in-part.
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STATEMENT OF THE CASE
Claims 1, 3-5, 7-11, 13-15, 31, 45, 48, 49, and 52 are pending and on
appeal.
Claim 1 is representative of the subject matter on appeal:
1. A particle, comprising:
a material comprising a polymer backbone bonded to a chemical
species via a 1,2,3-triazole group the particle has a maximum dimension of
at most 5,000 microns.
The Examiner relies on the following evidence:
Lanphere et al. US 2004/0096662 A1 May 20, 2004
Hartmuth C. Kolb & K. Barry Sharpless, The growing impact of click
chemistry on drug discovery, 24 DRUG DISCOVERY TODAY 1128-1137
(2003).
Maisie J. Joralemon et al., Shell Click-Crosslinked (SCC) Nanoparticles: A
New Methodology for Synthesis and Orthogonal Functionalization, 127
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 16892-16899 (2005).
Dmitri A. Ossipov & Jöns Hilborn, Poly(vinyl alcohol)-Based Hydrogels
Formed by “Click Chemistry”, 39 MACROMOLECULES 1709-1718 (2006).
The claims stand rejected as follows:
I. Claims 1, 3-5, 7, 10, 11, 13, 14, and 31 under 35 U.S.C.
§ 103(a) as unpatentable over Joralemon (Ans. 8-9).
II. Claims 1, 3-5, 7-11, 13-15, 31, 45, 48, 49, and 52 under 35
U.S.C. §103(a) as unpatentable over Lanphere and Joralemon (Ans. 9-10).
III. Claims 1, 3-5, 7-10, 13-15, 31, 45, 48, 49, and 52 under 35
U.S.C. §103(a) as unpatentable over Lanphere and Ossipov (Ans. 4-6).
IV. Claim 11 under 35 U.S.C. §103(a) as unpatentable over
Lanphere, Ossipov, and Kolb (Ans. 6-7).

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PRINCIPLES OF LAW
A rejection on the ground of obviousness must include “articulated
reasoning with some rational underpinning to support the legal conclusion of
obviousness.” In re Kahn, 441 F.3d 977, 988 (Fed. Cir. 2006). “[T]his
analysis should be made explicit” and it “can be important to identify a
reason that would have prompted a person of ordinary skill in the relevant
field to combine the elements in the way the claimed new invention does.”
KSR Int’l Co., v. Teleflex Inc., 550 U.S. 398, 418 (2007).
FINDINGS OF FACT
1. Joralemon discloses that “[c]lick chemistry between an alkynyl
shell functionalized block copolymer micelle [i.e., a micelle formed from an
amphiphilic diblock copolymer of poly(acrylic acid)80-b-poly(styrene)90] and
an azido terminated dendrimer was employed to construct crosslinks
between the polymer chain segments within the micelle corona, to yield
shell Click-crosslinked (SCC) nanoparticles” (Joralemon Abstract; 16899,
col. 1). The polymers in the resultant nanoparticles are cross-linked via
1,2,3-triazole groups, and have average diameters well below 5,000 microns,
as shown in Table 1 below:

(Joralemon 16897, Table 1.)
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2. Joralemon further teaches that “[t]his type of nanoparticle
crosslinking and subsequent functionalization provides a facile route for the
future attachment of biologically important molecules, therapeutics, and
targeting ligands onto the nanoparticle” (Joralemon 16899, col. 2).
3. Lanphere discloses polymeric particles “having a diameter of
about 500 microns or less . . . [with] a first density of pores in an interior
region and a second [different] density of pores at a surface region” or “a
first average pore size in an interior region and a second [different] average
pore size at the surface region” (Lanphere ¶¶ 4, 5). For example, the density
of pores in the center of the particle may be greater than the density of pores
at the surface of the particle, or pores near the center of the particle may be
relatively large, and pores near the surface may be relatively small (id. at ¶¶
54, 62). According the Lanphere, this variation in pore size and/or density
affects various properties of the particles, including compressibility and
resistance to shear forces and abrasion (id. at ¶¶ 54, 55).
4. Lanphere‟s particles “are substantially formed of a polymer,
such as . . . a high molecular weight polyvinyl alcohol (PVA) . . . [and] a
minor amount . . . of a gelling material . . . such as [an] alginate” (Lanphere
¶ 53). Essentially, the base polymer and gelling material are combined,
formed into droplets and solidified, and then the polymer in the solid drops
is reacted with “an agent that chemically reacts with the base polymer to
cause cross-linking between polymer chains and/or within a polymer chain”
(id. at ¶¶ 84, 85). “For polyvinyl alcohol,” the cross-linking agent “includes
one or more aldehydes, such as formaldehyde . . . and glutaraldehyde (id. at
¶ 85).
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5. According to Lanphere, the cross-linking agent “diffuses into
the solid drops from the surface of the particle in a gradient which . . .
provides more cross-linking near the surface of the solid drop than in the
body and the center of the drop . . . providing a stiff, abrasion-resistant
exterior” (Lanphere ¶ 85).
6. Ossipov teaches that “[c]hemically cross-linked PVA
[poly(vinyl alcohol)] hydrogels have been mostly prepared using
bifunctional cross-linking agents, such as glutaraldehyde . . . which react
directly with PVAs hydroxyl groups” (Ossipov 1712, col. 1), but “cross-
linking with low-molecular-weight toxic reagents is not practicable for in-
situ hydrogel formation” (id.).
7. Ossipov discloses an alternative method, “which could afford
in-vivo hydrogel formation” (Ossipov 1709, col. 1), in which hydrogels are
prepared by “click chemistry” (id. at 1711, col. 2 (emphasis omitted)), i.e.,
by mixing “alkyne- and azide-modified PVAs . . . in the presence of Cu
+

catalyst” (id.). According to Ossipov, “chemoselective 1,3-cycloaddition
between alkynyl and azido functional groups of PVA components . . .
[resulted in] the multiple formation of triazole cross-links” (id. at 1712, col.
1; Figure 4A).
8. Ossipov teaches that the click-chemistry technique produces
“solid, uniform hydrogels” (Ossipov 1718, col. 1). Ossipov does not
disclose particles of any kind made from the PVA hydrogels.

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DISCUSSION
I.
Claims 1, 3-5, 7, 10, 11, 13, 14, and 31 stand rejected as unpatentable
over Joralemon.
The Examiner‟s position is that the claimed invention would have
been obvious because Joralemon “teaches nanoparticles of poly(acrylic
acid)-block-styrene that are cross-linked via 1,2,3-triazoles” (Ans. 8), and
also suggests “[i]ncorporation of a drug, and attaching the drug to the
nanoparticle, including covalent attachment to the 1,2,3-triazole” (id.).
Appellant contends that Joralemon “teaches amphiphilic diblock
copolymers of poly(acrylic acid)80-b-poly(styrene)90 that have been
assembled into micelles . . . [which] flatten onto a mica surface „when drop
deposited and allowed to dry freely in air . . . ‟” (App. Br. 6). Appellant
contends that “[o]ne skilled in the art would have known that such a
flattened micelle is not a particle” (Reply Br. 2).
This argument is not persuasive. As discussed above, Joralemon
explicitly describes the product of 1,2,3-triazole crosslinking between
alkynyl shell functionalized block copolymer micelles and azido terminated
dendrimers as SCC “nanoparticles” (FF1). The flattened shape of the
nanoparticles is irrelevant, as the claims do not require spherical particles.
The rejection of claims 1, 3-5, 7, 10, 11, 13, 14, and 31 as
unpatentable over Joralemon is affirmed.
II.
Claims 1, 3-5, 7-11, 13-15, 31, 45, 48, 49, and 52 stand rejected as
unpatentable over Lanphere and Joralemon.
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Again, the Examiner finds that Joralemon “teaches nanoparticles of
poly(acrylic acid)-block-styrene that are cross-linked via 1,2,3-triazoles”
(Ans. 8), and also suggests “[i]ncorporation of a drug, and attaching the drug
to the nanoparticle, including covalent attachment to the 1,2,3-triazole” (id.).
The Examiner further finds that Lanphere “teaches polyvinyl alcohol
. . . particles cross-linked with formaldehyde . . . [with] diameters from 300-
500 microns” (id. at 4).
The Examiner‟s position is that it would have been obvious to use a
1,2,3-triazole group to crosslink Lanphere‟s particles because Joralemon
provides evidence that “1,2,3-triazole groups are known functionalities for
crosslinking of nanoparticles used for drug delivery” (Ans. 10).
Appellant contends that “the chemicals used by Joralemon to obtain
his 1,2,5-triazole linkage are chemically incompatible with Lanphere‟s
polyvinyl alcohol” (App. Br. 7). Appellant contends that “Joralemon‟s
polymer contains polyacrylic acid, whose carboxylic acid group reacts with
propargylamine to form a precursor product that subsequently reacts with 1-
[3'-(dimethylamino)propyl]-3-ethylcarbodiimide methiodide to form the
1,2,3-triazole group when a copper sulfate catalyst is added” (id.). Appellant
contends that “one skilled in the art would readily appreciate[] [that]
Lanphere‟s polyvinyl alcohol (PVA) does not react with Joralemon‟s
propargylamine to form the precursor product needed for formation of the
1,2,3-triazole group” (id.).
Appellant‟s argument is persuasive with respect to dependent claim
15, the only claim on appeal actually limited to particles made of cross-
linked polyvinyl alcohol backbones, and we will reverse the rejection with
respect to this claim.
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However, Appellant‟s argument is not persuasive with respect to
claims 1, 3-5, 7-11, 13, 14, 31, 45, 48, 49, and 52. As discussed above,
Appellant‟s arguments with respect to Joralemon do not persuade us that
claims 1, 3-5, 7, 10, 11, 13, 14, and 31 are patentable over Joralemon alone.
Moreover, Appellant‟s arguments, whether in response to this rejection over
Lanphere and Joralemon, or the previous rejection over Joralemon alone, are
not relevant to the limitations of claims 8, 9, 45, 48, 49, and 52.
The rejection of the claims as unpatentable over Lanphere and
Joralemon is reversed with respect to claim 15, and affirmed with respect to
claims 1, 3-5, 7-11, 13, 14, 31, 45, 48, 49, and 52.
III.
Claims 1, 3-5, 7-10, 13-15, 31, 45, 48, 49, and 52 stand rejected as
unpatentable over Lanphere and Ossipov.
The Examiner finds that Lanphere “teaches polyvinyl alcohol . . .
particles cross-linked with formaldehyde . . . [with] diameters from 300-500
microns” (Ans. 4). The Examiner finds that Lanphere‟s particles “may be
porous” and that “Lanphere suggests the delivery of drugs . . . which may be
in or on the particle[s]” (id.). The Examiner finds that Lanphere “does not
teach cross-linking by a 1,2,3-triazole group” (id.).
However, the Examiner finds that Ossipov “teaches cross-linked
polyvinyl alcohol through a 1,2,3-triazole group” and also “teaches that the
method . . . is advantageous over previously known methods of cross-linking
PVA with toxic crosslinkers such as glutaraldehyde which is toxic and
therefore unsuitable for in vivo crosslinking” (id. at 5).
The Examiner concludes that it would have been obvious “to have
used the cross-linking method of Ossipov to cross-link the PVA particle of
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Lanphere, thereby resulting in cross-links that contain the 1,2,3-triazole
group structure” (id.), “instead of using an aldehyde for cross-linking as it
eliminates the use of toxic substances” (id.).
Appellant contends that “it would not have been obvious to modify
Lanphere based on Ossipov” because Lanphere‟s objective was to produce
an embolic particle with variable pore sizes in different regions of the
particle, e.g., with small pores near the surface of the particle, to make the
particle relatively stiff and incompressible, and enhance resistance to shear
forces and abrasion (App. Br. 3-4), while “Ossipov‟s cross-linked product is
described as a solid, uniform hydrogel” (id. at 4).
Appellant‟s argument is persuasive. Lanphere uses an extrinsic cross-
linker to diffuse into pre-gelled particles in order to form non-uniformly
cross-linked particles with variable pore sizes and/or densities in different
regions of the particles (FFs 3-5). Ossipov, on the other hand, forms a
uniform hydrogel “by simply mixing . . . the prepared PVA components in
the presence of Cu
+
catalyst” (Ossipov 1711, col. 2; FF7), and in any case,
does not form particles at all (FF8). The Examiner has not explained how or
why one of ordinary skill in the art would use Ossipov‟s click chemistry
technique, in which functionalized polymers self-cross-link to form a solid,
uniform structure, to form Lanphere‟s heterogeneous, non-uniformly cross-
linked embolic particles.
The rejection of claims 1, 3-5, 7-10, 13-15, 31, 45, 48, 49, and 52 as
unpatentable over Lanphere and Ossipov is reversed.

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IV.
Claim 11 stands rejected as unpatentable over Lanphere, Ossipov, and
Kolb.
The Examiner relies on Lanphere and Ossipov as above, and cites
Kolb as evidence that that “the covalent binding of drugs to the triazole
reaction product of an azide and [an] alkyne” was known in the art (Ans. 6).
As Kolb does not cure the underlying deficiency in the proposed
combination of Lanphere and Ossipov, we will reverse this rejection as well.
SUMMARY
I. The rejection of claims 1, 3-5, 7, 10, 11, 13, 14, and 31 as
unpatentable over Joralemon is affirmed.
II. The rejection of claims 1, 3-5, 7-11, 13-15, 31, 45, 48, 49, and
52 as unpatentable over Lanphere and Joralemon is reversed with respect to
claim 15, and affirmed with respect to claims 1, 3-5, 7-11, 13, 14, 31, 45, 48,
49, and 52.
III. The rejection of claims 1, 3-5, 7-10, 13-15, 31, 45, 48, 49, and
52 as unpatentable over Lanphere and Ossipov is reversed.
IV. The rejection of claim 11 as unpatentable over Lanphere,
Ossipov, and Kolb is reversed.
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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