Ex Parte Harris et al

Patent Trial and Appeal Board

Apr 27, 2017

13155111 (P.T.A.B. Apr. 27, 2017)

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.
13/155,111 06/07/2011 Anthony Harris UVMO.P0048US/11104628 2351
32425 7590 05/01/2017
NORTON ROSE FULBRIGHT US LLP
98 SAN JACINTO BOULEVARD
SUITE 1100
AUSTIN, TX 78701-4255
EXAMINER
LAZARO, DOMINIC
ART UNIT PAPER NUMBER
1611
NOTIFICATION DATE DELIVERY MODE
05/01/2017 ELECTRONIC
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.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
aoipdocket @ nortonrosefulbright .com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ANTHONY HARRIS, JONATHAN THOMPSON,
REBECCA RONE, SHEILA GRANT, and DAVID GRANT1
Appeal 2015-007166
Application 13/155,111
Technology Center 1600
Before DEMETRA J. MILLS, JOHN G. NEW, and RICHARD J. SMITH,
Administrative Patent Judges.
NEW, Administrative Patent Judge.
1 Appellants state the real party-in-interest is The Curators of The University
of Missouri. App. Br. 1.
Appeal 2015-007166
Application 13/155,111
DECISION ON APPEAL
Appellants file this appeal under 35 U.S.C. § 134(a) from the
Examiner’s Final Rejection of claims 1—3, 5, 6, 11, 12, 15—19, 33, 34, 36,
and 37, which stand rejected as unpatentable under 35 U.S.C. § 103(a) as
being obvious over the combination of over Atala et al. (US 2006/0257377
Al, November 16, 2006) (“Atala”), M.G. Bellino et al., Adsorption Kinetics
of Charged Thiols on Gold Nanoparticles, 6 Phys. Chem. Chem. Phys.,
424—28 (2004) (“Bellino”), Goldenberg et al. (US 2007/0264265 Al,
November 15, 2007) (Goldenberg”), Farokhzad et al. (WO 2010/042555 Al,
April 15, 2010) (“Farokhzad”), and L. Castaneda et al., Collagen Cross-
Linking with Au Nanoparticles, 9 Biomacromolecules 3383—88 (2008)
(“Castaneda”).
We have jurisdiction under 35 U.S.C. § 6(b).
We REVERSE.
NATURE OF THE CLAIMED INVENTION
Appellants’ invention is directed to compositions comprising collagen
covalently bound to particles, in which covalent bonds are formed between
reactive groups of the collagen and reactive groups of the particles, and the
particles have an average particle diameter ranging from 20 to 1000
nanometers. Abstract.
REPRESENTATIVE CLAIM
Claim 1 is representative of the claims on appeal and recites:
1. A composition comprising collagen covalently
bound to particles, wherein covalent amide bonds are formed
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Application 13/155,111
between free carboxylic acid groups of isolated or purified
collagen and amine reactive groups of the particles, wherein the
particles have an average particle diameter size ranging from 50
to 1000 nanometers, and wherein collagen is not cross-linked
through the particles, and wherein the particles comprise ceramic
material, biodegradable material, or metallic material of gold,
silver, platinum, titanium, nickel, or copper.
App. Br. 26.
ISSUE AND ANALYSIS
Issue
Appellants argue the Examiner erred because Castaneda as a whole
does not teach the Examiner’s asserted proposed modifications and teaches
away from the instantly claimed invention. App. Br. 8.
Analysis
The Examiner finds Castaneda teaches the cross-linking of collagen
with tiopronin-modified gold nanoclusters (“TPAu”) via EDC (N-(3
dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride, coupling. Final
Act. 10 (citing Castaneda 3384). The Examiner finds that, although
Castaneda’s teachings are directed to the preparation of collagen cross-
linked with gold particles, Castaneda also teaches general stoichiometric
conditions by which free amino groups and free carboxyl groups of collagen
may be utilized in attaching functionalized gold particles in light of intra-
and intermolecular cross-linking. Id. (citing Castaneda, Abstr., 3386). The
Examiner finds Castaneda explicitly notes that collagen possesses an
abundance of carboxyl groups for cross-linking with nanoparticles
containing amino functionalized nanoparticles and teaches varying amounts
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Application 13/155,111
of gold nanoparticles at varying mass and molar ratios of collagen, with
stoichiometric ratios for attaching only particles to collagen dendrimers
without cross-linking. Id. (citing Castaneda 3385, 3386, Tab. 1, Fig. 5). The
Examiner finds Castaneda also teaches collagen:gold nanoparticle molar
ratios resulting in less than 20% utilization of free amine groups, and
contemplates the utilization of this chemistry for amino functionalized gold
with collagen carboxyl groups. Id. (citing Castaneda 3386, Tab. 5).
Appellants argue that an objective reading of the teachings of
Castaneda, as a whole and from the perspective of one skilled in the art,
would motivate an increased concentration of nanoparticles in order to
increase cross-linking through the nanoparticles. App. Br. 8—9. Appellants
contend these teachings are distinct from linkage between collagen fibers
without cross-linking through the particles, as claimed by Appellants’
invention. Id. at 9.
Appellants assert that, when read as a whole, the goal of Castaneda is
to increase cross-linking between the collagen and the nanoparticles in order
to increase stability of the resulting structure. App. Br. 9 (citing Castaneda
3384). Appellants contend that, although Castaneda discusses
stoichiometric conditions by which free amino groups and free carboxyl
groups of collagen may be utilized in attaching functionalized gold particles,
the collective teachings of the article would lead a person of ordinary skill in
the art to increase the concentration of nanoparticles and decrease the
concentration of the collagen in order to increase cross-linking through the
particles — which in turn increases stability of the composition. Id. at 10
(citing Castaneda 3386). According to Appellants, Castaneda explicitly
teaches away from cross-linking between the collagen molecules by
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Application 13/155,111
describing the direct covalent cross-linking of two collagen molecules
without the involvement of the gold nanoparticles is “undesired.” Id. (citing
Castaneda 3384—85). Appellants argue further that Castaneda teaches
nanoparticles with surface amino groups could potentially be used to cross­
link the nanoparticles with collagen by using the abundant carboxylic acid
groups of collagen to bind. Id. (citing Castaneda 3386).
Appellants further observe that using the EDC carbodiimide coupling
reaction taught in Castaneda to produce peptide bonds between the
carboxylic acid groups found on the collagen and the amine groups on the
gold will also produce a non-specific reaction with hydroxyl groups on the
collagen fibers as well. App. Br. 10.
Appellants point to the passage relied upon by the Examiner as
teaching “varying amounts of gold nanoparticles at a varying mass and
molar ratios of collagen with stoichiometric ratios for only attaching
particles to collagen dendrimers without cross[-]linking.” App. Br. 10—11
(quoting Final Act. 10 (citing Castaneda 3386, Fig. 5)). Appellants contend
that a full reading of the passage cited by the Examiner teaches that: “it
appears that even after the addition of large amounts of nanoparticles (AU5
and AU6) the particles form cross-links rather than only attaching to
collagen.” Id. at 11 (citing Castaneda 3386). Appellants argue, therefore,
that Castaneda teaches that addition of the particles causes cross-linking
between the nanoparticles and collagen instead of just attaching the particles
to the collagen without cross-linking the collagen fibers. Id.
We think Appellants have the better position. Castaneda teaches:
The cross-linking of collagen is a way to improve the
mechanical stability and to slow down the biodegradation rate.
For these reasons, several cross-linking procedures ... have been
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Application 13/155,111
developed. Many of the chemical cross-linking methods
incorporate a bridge molecule as a part of the cross-link. Another
way to cross-link collagen chemically is to use so-called zero-
length linkers, coupling agents capable of forming peptide bonds
between collagen molecules. EDC (l-ethyl-3-(3-dimethyl
aminopropyl) carbodiimide) is one such coupling agent.
Castaneda 3383 (internal references omitted). Castaneda thus teaches at
least two methods of cross-linking collagen: (1) the use of linker, or
bridging molecules; and (2) the direct formation of peptide bonds between
collagen molecules via a coupling agent such as EDC. Claim 1 of
Appellants’ application recites, in relevant part (emphasis added): “wherein
collagen is not cross-linked through the particles,” thereby explicitly
excluding method (1) of Castaneda.
The method taught by Castaneda comprises:
[A] novel approach to collagen cross-linking on the basis of
tiopronin-modified gold [TPAu] nanoparticles. Multiple
carboxyl groups are present on the surface of Au nanoparticles,
thus nanoparticles are capable of forming the multiple crosslinks
with the collagen. The formation of the peptide bonds with
amino groups of collagen is achieved via EDC coupling.
Id. The use of EDC coupling directly suggests that the method will form
peptide bonds directly between the collagen polymers, as taught by method
(2) of Castaneda, supra.
However, Castaneda expressly seeks to minimize or eliminate direct
peptide bond cross-linking between collagen molecules, and to promote
maximum use of TPAu nanoparticles as a bridging molecule between the
collagen molecules. Specifically, Castaneda teaches: “Cross-linking of
collagen has been extensively studied. Most of the cross-linking processes
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involve a two-point link between the collagen molecules. Here we employ
TPAu to serve as a linking agent because of its ability to form more then
[sic] two bonds with the collagen molecules.” Castaneda 3384 (emphasis
added). Castaneda further teaches:
The cross-linking of collagen with TPAu was performed via the
EDC carbodiimide coupling reaction, as shown in Figure 1,
reaction 2. To promote the reaction between TPAu carboxylic
groups and the collagen amino moieties while at the same time
limiting the EDC promoted self-cross-linking of collagen, we
used a low concentration of collagen and an excess of EDC
without NHS. The undesired side reaction that occurs under
these conditions and results in the cross-linking of two collagen
molecules without the involvement of TPAu is at the level of 2.3
± 0.4%, as described later in the text.
Id. at 3383—84 (emphases added). Castaneda thus teaches using TPAu as a
bridging molecule is the desired outcome and that direct peptide bond, EDC-
mediated cross-linking between collagen molecules is expressly undesirable.
Castaneda teaches that using TPAu as a bridging molecule is a desirable
outcome because: “[CJollagen cross-linking with nanoparticles containing
surface amino groups could potentially result in increased cross-linking
density. Such a strategy would enable the reaction between abundant
collagen carboxyl groups and the nanoparticle amino groups, resulting in a
higher cross-linking density.” Id. at 3386 (emphasis added).
A reference teaches away when “a person of ordinary skill, upon
reading the reference, would be discouraged from following the path set out
in the reference, or would be led in a direction divergent from the path that
was taken by the applicant.” In re Gurley, 27 F.3d 551, 553 (Fed. Cir.
1994). Castaneda teaches that using TPAu nanoparticles as a bridging
molecule is a desired outcome and that direct EDC-mediated cross-linking
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Application 13/155,111
between collagen molecules is an “undesired” side reaction. We agree with
Appellants that the teachings of Castaneda would discourage or divert a
person of ordinary skill from following the path set out in the Appellants’
claims, i.e., “wherein collagen is not cross-linked through the particles”
(emphasis added).
Moreover, even were we to assume, arguendo, that Castaneda does
not expressly “teach away,” in the sense of Gurley, from Appellants’
claimed invention, Castaneda nevertheless fails to either teach or suggest the
disputed limitation, nor does the Examiner cite to any other reference that
expressly teaches or suggests it. Indeed, as we have explained, Castaneda
expressly teaches the opposite of cross-linking collagen “wherein collagen is
not cross-linked through the particles.” Quite the opposite, in fact:
Castaneda seeks to maximize the bonds between the bridging TPAu
molecules and collagen; stating that such is a desirable outcome because it
“could potentially result in increased cross-linking density.” Castaneda
3386.
Because we find this issue dispositive of the appeal, we do not reach
Appellants’ additional arguments. We consequently reverse the Examiner’s
rejection of the claims.
DECISION
The Examiner’s rejection of claims 1—3, 5, 6, 11, 12, 15—19, 33, 34,
36, and 37 under 35 U.S.C. § 103(a) is reversed.
REVERSED
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