Ex Parte Davis et al

Patent Trial and Appeal Board

Jul 9, 2018

12064063 (P.T.A.B. Jul. 9, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
12/064,063 06/24/2008
24504 7590 07/11/2018
THOMAS I HORSTEMEYER, LLP
3200 WINDY HILL ROAD, SE
SUITE 1600E
ATLANTA, GA 30339
FIRST NAMED INVENTOR
Benjamin Guy Davis
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
820908-1090 5360
EXAMINER
DONOHUE, SEAN R
ART UNIT PAPER NUMBER
1618
NOTIFICATION DATE DELIVERY MODE
07/11/2018 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):
uspatents@tkhr.com
ozzie. liggins@tkhr.com
docketing@thomashorstemeyer.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte BENJAMIN GUY DA VIS, SANDER IZAAK VAN KASTEREN,
DANIEL ANTHONY, and NICOLA SIBSON
Appeal2017-004955
Application 12/064,063 1
Technology Center 1600
Before JOHN G. NEW, RICHARD J. SMITH, and DAVID COTTA,
Administrative Patent Judges.
COTTA, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a
composition comprising a conjugate. The Examiner rejected the claims on
appeal as obvious under 35 U.S.C. § 103(a).
We affirm.
1 According to Appellants, the real party in interest is Oxford University
Innovation Limited, a wholly owned subsidiary of the University of Oxford.
App. Br. 3.
Appeal2017-004955
Application 12/064,063
STATEMENT OF THE CASE
The Specification discloses that "[a] variety of imaging techniques are
available for diagnostic purposes." Spec. 1. "Contrast agents are used in
imaging to increase the signal difference between the area of interest and
background." Id. According to the Specification, "[ o ]ne type of contrast
agent that is used is super magnetic particles," which are "iron containing
colloidal particles, made of iron oxides and hydroxides." Id. The
Specification asserts "[t]he present invention provides a conjugate
comprising an iron containing colloidal particle, the particle being
conjugated to one or more targeting moieties." Id.
Claims 1-11 and 33-55 are on appeal. Claim 1 is illustrative and
reads as follows:
1. A composition comprising a conjugate, wherein the
conjugate comprises an iron containing colloidal particle
conjugated to one or more targeting moieties, and
wherein at least one of the targeting moieties is an
oligosaccharide, which comprises a functionalized
saccharide unit wherein one or more hydroxyl groups on
an unfunctionalized saccharide unit is replaced by a
group selected from the group consisting of hydrogen,
halogen, mercapto, C1-6 alkoxy, C1-6 alkylthio, -COOR'
wherein R' is hydrogen or a C1-6 alkyl group, amino C1-6
alkylamino, di(C1-6)alkylamino, C1-6 acetylamino, di (C1-
6) acetylamino and phosphate, where the conjugate is
produced by a process, the process comprising:
a) providing a compound of formula (I):
R1-S-CH2CN (I)
wherein R1 is an acetylated carbohydrate-based
moiety;
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Application 12/064,063
App. Br. 28.
b) selectively deprotecting the compound of
formula (I), thereby converting the acetylated
groups to hydroxyl groups;
c) reacting the product of step (b) with a
carbohydrate processing enzyme, thereby
extending the compound of formula (I) by the
addition of one or more carbohydrate-based
moieties R2; and
d) activating the product of step ( c ), thereby
producing a compound of formula (II):
(R2)n-R1-S-CH2-C(NH)-O-Me (II)
wherein n is the number of carbohydrate-based
moieties R2 added in step ( c) and is an integer of
from 1 to 10.
The claims stand rejected as follows:
Claims 1 and 2 stand rejected under 35 U.S.C. § 103 as being
unpatentable over the combination of Josephson, 2 Palmacci, 3 Menz, 4 and
Palcic. 5
2 Josephson et al., US Patent Publication No. 2003/0092029 Al, published
May 15, 2003 ("Josephson").
3 Palmacci et al., US Patent No. 5,262,176, issued Nov. 16, 1993
("Palmacci").
4 Menz et al., US Patent No. 5,352,432, issued Oct. 4, 1994 ("Menz").
5 Palcic et al., Chemoenzymatic Synthesis of Dendritic Sialyl LewisX, 305
Carbohydrate Research 433--442 (1998) ("Palcic").
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Application 12/064,063
Claims 1-11 and 33-55 stand rejected under 35 U.S.C. § 103 as being
unpatentable over the combination of Josephson, Palmacci, Menz, Quay, 6
Raganathan, 7 Lee, 8 and Palcic.
OBVIOUSNESS OVER JOSEPHSON, P ALMACCI, MENZ AND
PALCIC
Appellants argue claims 1 and 2 together. We designate claim 1 as
representative.
Josephson discloses conjugates comprising a magnetic nanoparticle
linked to a binding moiety that can be used for detecting specific target
molecules in sample solutions. Josephson ,r 10. The binding moiety in
Joshephson's conjugate "binds to a target in a sample, such as a nucleic acid
or protein, to another binding moiety on another conjugate, or to an
aggregation inducing molecule, such as avidin." Id. With respect to the
magnetic nanoparticle, Josephson discloses:
Dextran coated nanoparticles can be made and cross-linked
with epichlorhydrin. The addition of ammonia will react with
epoxy groups to generate amine groups. . . . This material is
known as cross-linked iron oxide or "CLIO" and when
functionalized with amine is referred to as amine-CLIO or NH2-
CLIO.
Id. ,r 73. With respect to the binding moiety, Josephson discloses:
6 Quay et al., EP O 727 255 A2, published Aug. 21, 1996 ("Quay").
7 Raganathan et al., US Patent Publication No. 2004/0097403 Al, published
May 20, 2004 ("Raganathan").
8 Lee et al., 2-Imino-2-Methoxyethyl 1-Thioglycosides: New Reagents for
Attaching Sugars to Proteins, 15(18) Biochemistry 3956-63 (1976) ("Lee").
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Application 12/064,063
A generally useful method of accomplishing linking is to
couple avidin to a magnetic nanoparticle and react the avidin-
nanoparticle with commercially available biotinylated
polysaccharides, to yield polysaccharide-nanoparticle
conjugates. For example, sialyl Lewis based polysaccharides
are commercially available as biotinylated reagents and will
react with avidin-CLIO .... The sialyl Lewis x tetrasaccharide
(Slex) is recognized by proteins known as selecin[], which are
present on the surfaces of leukocytes and function as part of the
inflammatory cascade for the recruitment of leukocytes.
Id. ,I 106.
Palmacci discloses methods for the synthesis of polysaccharide
covered superparamagnetic iron oxide colloids. Palmacci, col. 1, 11. 24--26.
Palmacci further discloses "[ w ]hen dextran is used in the process, a colloid
with a long plasma half-life after injection is obtained, and the colloid may
be utilized as an MR contrast agent." Id. at col. 5, 11. 28-30.
Menz discloses compositions that serve as contrast agents for the
enhancement of magnetic resonance images. Menz, col. 6, 11. 13-30.
Ligands useful in Menz's compositions include mono-, di, and oligo-
saccharides. Id. col. 7, 11. 45-55.
Palcic discloses E selectins among a family of transmembrane
glycoproteins responsible for adhesion to leukocytes. Id. at 433. Palcic
further discloses that sialyl Lewis x tetrasaccharide (Slex) and related
oligosaccharides are "lead compounds for that pharmaceutical industry
interested in the development of drugs for inflammatory diseases." Id.
In finding the composition of claim 1 to be obvious, the Examiner
articulates the basis for finding the claimed composition obvious over the
cited art in two ways. First, the Examiner concludes:
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Application 12/064,063
the teachings of Josephson alone make obvious a composition
comprising a conjugate, wherein the conjugate comprises as
iron oxide containing colloidal particle conjugated to one or
more targeting moieties, and wherein one of the targeting
moieties is an oligosaccharide which comprise[s] a saccharide
unit selected as N-acetyl glucosamine (GlcN-Ac), and wherein
the targeting moieties are selected from Sialyl Lewis X
(GlcNAc(-Fuc )-Gal-Sia).
Ans. 7; see also, Final Act. 9 6 ("Palmacci was merely used to teach that the
CLIOs Josephson is referring to as represented by [paragraph 112 of
Josephson] are colloidal cross-linked nanoparticles"). Second, the Examiner
concludes:
It would have been obvious to one of ordinary skill in the art at
the time of invention to modify the compositions taught by
Palmacci et al. (i.e., dextran covered colloidal particles cross
linked with epichlorohydrin) by simply adding ammonia to give
NH2-CLI0s and simply adding 2-imino-2-methoxyethyl-1-thio
functionalized Sialyl Lewis tetrasaccharide (Selx) as taught by
Josephson et al., Menz et al., and Palcic et al. because it would
advantageously enable robust covalent attachment to targeting
moiety and advantageously enable enhanced visualization of
leukocytes using MR imaging.
Non-Final Office Action10 8-9.
We agree with the Examiner that the cited art renders the claimed
composition obvious. We address Appellants' arguments below.
Appellants argue that the Examiner improperly switched the order of
the references during prosecution, alternately relying on Palmacci and then
on Josephson as the primary reference. Reply Br. 4--5. Appellants then
9 Office Action mailed April 19, 2016 ("Final Act.").
10 Office Action mailed November 26, 2013 ("Non-Final Act.").
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assert that Pahnacci "should be viewed as a primary reference for purposes
of analysis that is modified by Josephson." Id. at 5. In the event the Board
declines to treat Palmacci as the primary reference, Appellants assert that the
"finality of the Office Action was premature because new grounds of
rejection were ... presented, or in the alternative, the basis of rejection was
not properly communicated such that the issues could be clearly identified
precluding the Appellant from a fair and full opportunity to reply prior to
appeal." Id.
While we acknowledge that the Examiner has articulated the basis for
obviousness in two different ways, we are not persuaded that it merits
reversal or designation of a new ground of rejection. As an initial matter,
the finality of the Examiner's final rejection is not properly before us. See
MPEP § 2272 ("In the event that the patent owner is of the opinion that ... a
final rejection is improper or premature ... the patent owner may file a
petition under 37 CPR 1.181 requesting that the final rejection be withdrawn
and that prosecution be reopened."); MPEP § 1002.02; In re Mindick, 371
F.2d 892, 894 (CCPA 1967). 11 Moreover, once on appeal, changing the
number of references relied upon or the order of references cited does not
require a new ground of rejection where the examiner relies on the same
teachings from those references. See, MPEP § 1207.03(a)(II)(3) ("If the
examiner's answer removes one or more references from the statement of
11 The Board's primary role is to review adverse decisions of examiners
including the findings and conclusions made by the examiner. See Ex Parte
Frye, 94 USPQ2d 1072, 1077 (BPAI 2010) citing 37 C.F.R. § 4I.50(a)(l)
("The Board, in its decision, may affirm or reverse the decision of the
examiner in whole or in part on the grounds and on the claims specified by
the examiner.").
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rejection under 35 U.S.C. 103, and relies on the same teachings of the
remaining references to support the 35 U.S.C. 103 rejection, then the
rejection does not constitute a new ground of rejection."); MPEP §
1207.03(a)(II)(4) ("If the examiner's answer changes the order of references
in the statement of rejection under 35 U.S.C. 103, and relies on the same
teachings of those references to support the 35 U.S.C. 103 rejection, then the
rejection does not constitute a new ground of rejection.").
Appellants contend that Palmacci teaches the use of a homogeneous
colloid solution having small particles (up to 220 nm in size) as a solution to
problems associated with using heterogeneous colloid solutions that include
large particles. App. Br. 20. Appellants further contend that Josephson
teaches conjugates that "change aggregation state depending on the presence
or absence of a target molecule." Id. at 20-21. Appellants then assert that
the resulting aggregates of conjugates are heterogeneous and "greater than
500 nm in size." Based on these teachings, Appellants argue that "the large
aggregate disclosed in Josephson would change the principle of operation in
Palmacci and render Palmacci inoperable and unsuitable for its intended
use." Id. at 21. We are not persuaded.
As an initial matter, we note that Appellants' argument appears to
have no application to the Examiner's articulation of obviousness wherein
"Palmacci was merely used to teach that the CLIOs Josephson is referring to
as represented by [paragraph 112 of Josephson] are colloidal cross -linked
nanoparticles" - i.e., where Josephson is used as the primary reference.
Final Act. 7.
With respect to the Examiner's articulation of obviousness relying
upon Palmacci as the primary reference, we do not consider the size of
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Josephson's conjugates to require a change in the principles by which
Pahnacci operates. Both Pahnacci and Josephson disclose supermagnetic
iron oxide colloids that can be used as magnetic resonance contrast agents
and for detecting proteins and nucleic acids. Ans. 6; Palmacci col. 1, 11. 24--
26, col. 5, 11. 28-30; Josephson Abstract. Appellants have not provided
persuasive evidence that modifying the compositions taught by Palmacci in
the manner proposed by the Examiner (see Non-Final Act. 8-9) would
change the way in which the supermagnetic iron oxide colloids act as
contrast agents.
Moreover, Appellants do not provide persuasive evidence that
Palmacci's concerns regarding particle size would apply to Josephson's
conjugates. Palmacci's concerns regarding particle size relate to issues that
arise before the conjugates interact with the target molecule. See, Palmacci
col. 1, 1. 47 - col. 2, 1. 4 (noting that colloids that have been "sterilized by
passage through a 220 nm filter ... meet the current legal requirement for
sterility of parenteral pharmaceutical products" and discussing the difficulty
of characterizing heterogeneous colloids to ensure detection of sources of
toxicity). Appellants argue that Josephson's conjugates aggregate to form
large molecules in the size range that Palmacci identifies as being of
concern. App. Br. 20-21. However, as the Examiner explains, Josephson's
conjugates aggregate upon interaction with a target molecule, which
suggests that they "exist in the monodispersed state in solution prior to
interaction with a target molecule." Ans. 6. Appellants do not provide
persuasive evidence that the size of Johnson's monodispersed-i.e. non-
aggregated - conjugates are in the size range that Palmacci identifies as
being of concern. While Appellants argue that "it cannot be that [ the
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monodispersed state of Josephson's colloids] exists other than theoretically"
(App. Br. 22), Appellants do not provide evidence to support this argument.
See, Johnston v. IVAC Corp., 885 F.2d 1574, 1581 (Fed. Cir. 1989)
("Attorneys' argument is no substitute for evidence."); In re Pearson, 494
F.2d 1399, 1405 (CCPA 1974).
Appellants argue that "even if monodispersed conjugate states exist
that could be used as a contrast agent, once inside the body they would
quickly form heterogeneous aggregates with target molecules" and that this
would "change the principle of operation in Palmacci." Id. at 22-23. We
are not persuaded because Appellants do not provide persuasive evidence
that forming large heterogeneous aggregates upon interaction with a target
violates Palmacci's principle of operation. Appellants cite Palmacci's
teaching that "at the upper size limit, aggregates of superparamagnetic iron
oxide crystals are produced, but the aggregates vary over a narrow size
range" which "permits the colloids to be filter screened." App. Br. 20
( citing Palmacci col. 5, 11. 24--2 7). But, this discussion relates to Palmacci' s
colloids before they are used as a contrast agent or to detect proteins or
nucleic acids - i.e. before they encounter target molecules.
Appellants argue that Menz teaches MRI contrast agents designed to
increase uptake by the liver and Palmac teaches that targeting the liver
results in short half-lives and is thus undesirable. App. Br. 23. We are not
persuaded because the Examiner relies upon Menz as teaching a 2-imino-2-
methoxyethyl linking group "to advantageously enable facile conjugat[ion]
to amino functionalized iron oxide nanoparticles." Ans. 8. Appellants have
not provided persuasive evidence that the use of such a linking group would
change the principal by which the conjugates of Palmacci and/or Josephson
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operate. Moreover, Pahnacci teaches that "[ w ]hen dextran is used in the
process, a colloid with a long plasma half-life after objection is obtained,
and the colloid may be utilized as an MR contrast agent." Palmacci col. 5,
11. 28-30.
Appellants argue that "Palcic is devoid of any disclosure referencing
imaging agents or MRI agents." App. Br. 24. We are not persuaded. One
cannot show non-obviousness by attacking references individually when the
rejection is based on a combination of references. In re Keller, 642 F .2d
413,425 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir.
1986) ("Non-obviousness cannot be established by attacking references
individually where the rejection is based upon the teachings of a
combination of references."). Here, Palmacci and Josephson both disclose
imaging agents.
Accordingly, we affirm the Examiner's rejection of claim 1. While
Appellants provide a separate heading for claim 2, they do not provide
separate arguments. See, App. Br. 24. Claim 2 thus falls with claim 1.
OBVIOUSNESS OVER JOSEPHSON, P ALMACCI, MENZ, QUAY,
RAGANATHAN, LEE, AND PALCIC
Appellants argue independent claims 1, 4, 40, and 54 together. We
designate claim 1 as representative.
Appellants repeat their arguments that "the combination of Palmacci
with Josephson, Menz, and Palcic changes the principle of operation of
Palmacci and/or would render Palmacci unsuitable for its intended purpose."
App. Br. 25. Appellants then argue that neither Quay nor Ranganathan
teaches or suggests otherwise. As Appellants do not provide any new
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argument with respect to this rejection, we affirm the Examiner's rejection
of claim 1 for the reasons discussed above. Claims 4, 40, and 54 were not
argued separately and fall with claim 1. Appellants provide a separate
heading for dependent claims 2-3, 5-11, 33-39, 41-53, and 55, but do not
provide separate arguments. See, App. Br. 26. Claims 2-3, 5-11, 33-39,
41-53, and 55 thus fall with claim 1.
SUMMARY
For the reasons set forth herein, and those set forth in the Examiner's
Final Office Action and Answer, we affirm the Examiner's decision to reject
claims 1 and 2 under 35 U.S.C. § 103 as obvious over the combination of
Josephson, Palmacci, Menz, and Palcic and the Examiner's decision to reject
claims 1-11 and 33-55 under 35 U.S.C. § 103 as obvious over the
combination of Josephson, Palmacci, Menz, Quay, Raganathan, Lee, and
Palcic.
AFFIRMED
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