Weiguang Wang

Patent Trials and Appeals Board

Oct 7, 2019

13991608 - (D) (P.T.A.B. Oct. 7, 2019)

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.
13/991,608 09/24/2013 Weiguang Wang 4237.10WOUS 3055
24113 7590 10/07/2019
PATTERSON THUENTE PEDERSEN, P.A.
80 SOUTH 8TH STREET
4800 IDS CENTER
MINNEAPOLIS, MN 55402-2100
EXAMINER
KISHORE, GOLLAMUDI S
ART UNIT PAPER NUMBER
1612
MAIL DATE DELIVERY MODE
10/07/2019 PAPER
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.
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte WEIGUANG WANG

Appeal 2018-007231
Application 13/991,608
Technology Center 1600
____________

Before DONALD E. ADAMS, RICHARD M. LEBOVITZ, and
RYAN H. FLAX, Administrative Patent Judges.

ADAMS, Administrative Patent Judge.

DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from Examiner’s
decision to reject claims 7, 9–12, 14, 15, and 17–21. We have jurisdiction
under 35 U.S.C. § 6(b).
We AFFIRM.

1 We use the word “Appellant” to refer to “applicant” as defined in
37 C.F.R. § 1.42. Appellant identifies the real party in interest as University
of Wolverhampton (Appellant’s April 4, 2018 Appeal Brief (Appeal Br.) 2).
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Application 13/991,608

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STATEMENT OF THE CASE
Appellant’s disclosure “relates to a novel disulfiram, or derivative
thereof, formulation and uses thereof, in particular uses for the treatment of
cancer” (Spec.2 1: 11–12). Appellant’s claims 10, 14, 15, and 19 are
representative and reproduced below:
10. A method of treating breast cancer in a mammal by
inhibiting replication of cancer stem cells, the method
comprising:
providing a formulation comprising disulfiram,
diethyldithiocarbamic acid, or diethyldithiocarbamate (DDC)
encapsulated in a liposome, wherein the liposome increases an
in vivo half life of the disulfiram, diethyldithiocarbamic acid, or
DDC; and
administering the encapsulated formulation to the
mammal along with a copper containing formulation.
(Appeal Br. 22.)
14. A method of treating breast cancer comprising:
administering to a subject a therapeutically effective
amount of a disulfiram formulation comprising disulfiram,
diethyldithiocarbamic acid, or diethyldithiocarbamate (DDC),
encapsulated m a liposome that increases an in vivo half life of
the disulfiram, diethyldithiocarbamic acid, or
diethyldithiocarbamate (DDC).
(Id. at 23.)
15. The method of claim 14, wherein the method further
comprises: simultaneously or sequentially administering a
copper containing formulation, wherein the copper containing
formulation is not encapsulated in the liposome.
(Id.)

2 Appellant’s June 4, 2013 Specification.
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19. The method of claim 10, wherein the copper containing
formulation comprises copper gluconate.
(Id.at 24.)

Grounds of rejection before this Panel for review:
Claims 7, 9–12, 14, 15, and 17–21 stand rejected under 35 U.S.C.
§ 103(a) as unpatentable over Kennedy,3 in combination with Ito4 or
Lobler,5 and further in view of Leishman.6
Claims 19–21 stand rejected under 35 U.S.C. § 103(a) as unpatentable
over Kennedy, in combination with Ito or Lobler, and further in view of
Leishman, Ferrara,7 Slaga,8 and Bartunek.9

ISSUE
Does the preponderance of evidence relied upon by Examiner support
a conclusion of obviousness?

3 Kennedy, WO 2005/009338 A2, published Feb. 3, 2005.
4 Ito et al., Effects of Lipid Composition on the Transcorneal Penetration of
Liposomes Containing Disulfiram, a Potential Anti0cataract Agent, in the
Rabbit, 23 Biol. Pharm. Bull. 327–33 (2000).
5 Lobler et al., Drug delivery by nanoparticles – facing the obstacles, 22
IFMBE Proceedings 2335–38 (2008).
6 Leishman, US 2007/0148689 A1, published June 28, 2007.
7 Ferrara et al., US 2013/0090591 A1, Apr. 11, 2013.
8 Slaga et al., US 6,451,341 B1, issued Sept. 17, 2002.
9 Bartunek et al., US 2008/0248129 A1, published Oct. 9, 2008.
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FACTUAL FINDINGS (FF)
FF 1. Kennedy discloses the administration of disulfiram “in combination
with metal ions provides a pharmacologic approach to inhibiting cellular
proliferation of tumors” (Kennedy ¶ 15; Final Act.10 2–3; Ans.11 2–3).
FF 2. Kennedy discloses the treatment of cancers including breast cancer
(Kennedy ¶ 18; see also id. ¶ 43; Final Act. 2–3; Ans. 2–3).
FF 3. Kennedy discloses that “[s]uitable heavy metal ions include, inter
alia, copper” (Kennedy ¶ 15; see also id. ¶ 39; Final Act. 2–3; Ans. 2–3).
FF 4. Kennedy discloses, “[i]n a preferred embodiment, the heavy metal
ion is administered as a complex or chelate with . . . thiuram disulfide” and
“[i]n another preferred embodiment, the thiuram disulfide and the heavy
metal ion are administered in combination with another anticancer agent”
(Kennedy ¶ 16; Final Act. 2–3; Ans. 2–3).
FF 5. Kennedy discloses that the thiuram disulfide is preferably disulfiram
(Kennedy ¶ 38; Final Act. 2–3; Ans. 2–3).
FF 6. Kennedy discloses that “[t]he thiuram disulfide compound and the
heavy metal ion can be administered in combination or separately”
(Kennedy ¶ 39; Final Act. 2–3; Ans. 2–3).
FF 7. Kennedy discloses the delivery of its composition “using liposomes
as [a] carrier” (Kennedy ¶ 54; Final Act. 2–3; Ans. 2–3).
FF 8. Examiner finds that Kennedy “does not specifically teach the anionic
part of copper salt, such as ‘gluconate’” (Ans. 3; see Final Act. 3; see also
Ans. 4 (Examiner finds that although Kennedy “does not teach the addition
of copper as gluconate,” Kennedy “teaches copper sulfate”); Final Act. 8).

10 Examiner’s August 4, 2017 Final Office Action.
11 Examiner’s May 4, 2017 Answer.
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FF 9. Examiner finds that Ito and Lobler each disclose liposomal
formulations comprising disulfiram (Final Act. 3 (citing Ito, Abstract and
Materials and Methods; Lobler, Abstract and Materials and Methods); Ans.
3 (citing Ito, Abstract and Materials and Methods; Lobler, Abstract and
Materials and Methods)).
FF 10. Leishman discloses that “[l]iposomes can . . . be used to increase the
half-life of the active substance composition” (Leishman ¶ 189; see also
Ans. 3 (citing Leishman ¶¶ 156, 189, and 200) (Examiner finds that
“Leishman teaches that liposomes increase the half-life of active agents,”
wherein Leishman’s “active agents . . . are disulfiram and DDC”)).
FF 11. Examiner finds that Ferrara discloses “liposomal compositions for
cancer treatment” and “the use of either copper sulfate or copper gluconate”
(Ans. 4 (citing Ferrara Abstract; id. ¶¶ 10, 16, 157, and 233); see also Final
Act. 8 (citing Ferrara Abstract; id. ¶¶ 10, 16, 157, and 233)).
FF 12. Examiner finds that Slaga discloses “compositions containing
copper,” “that copper has protective effect against certain cancers,” and “the
addition of copper as copper sulfate or copper gluconate” (Ans. 4 (citing
Slaga Abstract and col. 9: 56 – 10: 2); see Final Act. 8 (citing Slaga Abstract
and col. 9: 56 – 10: 2)).
FF 13. Examiner finds that Bartunek discloses “compositions useful for
treating cancer and promoting cellular health” and “the use of copper
gluconate” (Ans. 4 (citing Bartunek Abstract, Tables, Claims, and ¶¶ 86 and
90); see Final Act. 8 (citing Bartunek Abstract, Tables, Claims, and ¶¶ 86
and 90)).

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ANALYSIS
The rejection over Kennedy, in combination with either Ito or Lobler, and
further in view of Leishman:
Based on Kennedy, in combination with Ito or Lobler, and further in
view of Leishman, Examiner concludes that, at the time Appellant’s
invention was made, it would have been prima facie obvious
to administer the compositions of disulfiram or
diethyldithiocarbamate in liposomes for the treatment of cancer
since it is art well-known that liposomes are sustained release
vehicles for the delivery of anti-cancer agents and [Kennedy] is
suggestive of the delivery of disulfiram or
diethyldithiocarbamate along with copper for the treatment of
cancer.
(Final Act. 3; see Ans. 3.) In this regard, Examiner reasons:
One of ordinary skill in the art would [have] be[en] motivated
to encapsulate the claimed compounds in liposomes
[because] . . . Ito and Labier [each] show the knowledge in the
art of encapsulating disulfiram in liposomes and Leishman
teaches that liposomes increase the half-life of active agents
such as disulfiram and DOC.
(Final Act. 3; see Ans. 3.) Examiner further reasons that although Kennedy
“does not specifically teach the anionic part of copper salt, such as
‘gluconate’,” because it is “the cationic part of the salt which is suggested by
[Kennedy] as being effective, it would have been obvious to one or ordinary
skill in the art to select any salt of copper, such as copper gluconate with a
reasonable expectation of success” (Final Act. 4; see Ans. 3).
The evidence on this record establishes that Kennedy discloses a
method of treating cancer, including breast cancer, comprising the
administration of disulfiram and a heavy metal ion, such as copper, in
combination or separately (FF 1–6). Thus, Kennedy discloses both
compounds recited in claim 10. Kennedy, Ito, and Lobler each disclose
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liposomal formulations comprising disulfiram and Leishman discloses that
“[l]iposomes can . . . be used to increase the half-life of [an] active
substance[, such as disulfiram and DDC,] composition” (FF 7, 9, and 10),
meeting the additional requirement of the claims that the disulfiram is
encapsulated in a liposome. Thus, we are not persuaded by Appellant’s
contention that the combination of Kennedy, Leishman and either Ito or
Lobler fails to suggest encapsulating an active substance, such as disulfiram
or DDC, in a liposome to increase its half-life or the administration of this
encapsulated disulfiram or DDC together with copper for the treatment of
breast cancer (see Appeal Br. 16 (citing Wang Decl.12); see also id. at 18–
20; Reply Br.13 2–4). Based on Leishman,, we find that one of ordinary skill
in the art would have known that the half-life of an active agent will be
increased when encapsulated in a liposome and that such a result is neither
unexpected nor surprising (see FF 10). Therefore, we are not persuaded by
Wang’s statement that an increase in the half-life of an active agent
encapsulated in a liposome is surprising (see Wang Decl. ¶ 8; see generally
id. ¶¶ 4–7).
For the foregoing reason, we are not persuaded by Appellant’s
contention that Kennedy, when viewed in isolation, failed to suggest the use
of a liposome to increase the half-life of an active agent (id. at 16–17). We
are also not persuaded by Appellant’s contention that Kennedy did not
appreciate that its liposome will increase the half-life of its active agent,
because Kennedy suggests “that to improve the half-life of an active
compound, it can be conjugated to a water soluble non-immunogenic high

12 Declaration of Weiguang Wang, signed October 7, 2017.
13 Appellant’s July 5, 2018 Reply Brief.
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molecular weight polymer to form a polymer conjugate, which can result in
a longer half-life of the active compound in the body” (id.). Initially, we
note that Appellant’s claims 10, 14, and 15 do not exclude a polymer
conjugate (see id. at 22). Further, Leishman supports a conclusion that those
of ordinary skill in this art at the time of Appellant’s claimed invention knew
that liposomes increase the half-life of active agents encapsulated therein
(see FF 10). In addition, even if the prior art did not recognize that
liposomes increased the half-life of an active agent, Kennedy discloses, as
Appellant appreciates, liposomes comprising disulfiram (FF 7; see also
Appeal Br. 16 (Appellant recognizes that Kennedy discloses the use of
“liposomes as a carrier”); Reply Br. 2 (“Applicant does not dispute that
Kennedy discloses liposomes as a delivery form for disulfiram, that Ito and
Lobler disclose liposomes containing disulfiram, and that Leishman teaches
that encapsulation of active agents such as disulfiram and DDC to increase
their half-life”)). “[T]he discovery of a previously unappreciated property of
a prior art composition, or of a scientific explanation for the prior art's
functioning, does not render the old composition patentably new to the
discoverer.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347 (Fed. Cir.
1999).
Kennedy discloses the administration of disulfiram and copper “in
combination or separately” (FF 6). Therefore, we are not persuaded by
Appellant’s contention that “Kennedy teaches that copper is preferably
administered as a complex with the active ingredient . . ., rather than
administered as a separate formulation, such as copper gluconate” (Appeal
Br. 17; see also id. at 17–18). See In re Lamberti, 545 F.2d 747, 750 (CCPA
1976) (A reference disclosure is not limited only to its preferred
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embodiments, but is available for all that it discloses and suggests to one of
ordinary skill in the art.). To be complete, we note that Appellant’s claims
10, 14, and 15 are not limited to copper gluconate.
For the foregoing reasons, we are not persuaded by Appellant’s
contention that Examiner’s rejection is based on improper hindsight (Appeal
Br. 18–20; see also Reply Br. 2).
The rejection of claims 10, 14, and 15 under 35 U.S.C. § 103(a) as
unpatentable over Kennedy, in combination with Ito or Lobler, and further in
view of Leishman, is affirmed. Claims 7, 9, 11, 12, 17, 19, and 20 are not
separately argued and fall with claim 10. Claims 18 and 21 is not separately
argued and falls with claim 14.

The rejection over Kennedy, in combination with Ito or Lobler, and further
in view of Leishman, Ferrara, Slaga, and Bartunek:
Based on Kennedy, in combination with Ito or Lobler, and further in
view of Leishman, Ferrara, Slaga, and Bartunek, Examiner concludes that, at
the time Appellant’s invention was made, it would have been prima facie
obvious “to use copper as copper gluconate instead of sulfate taught by
[Kennedy in combination with Ito or Lobler and further in view of
Leishman, because] . . . Ferrara and Slaga teach the equivalency between the
two salts of copper and that Bartunek teaches the addition of copper as
copper gluconate” (Final Act. 8; see also Ans. 4; see e.g., Appeal Br. 24
(Appellants’ claim 19)).
Kennedy discloses the administration of disulfiram and copper “in
combination or separately” (FF 6). A reference disclosure is not limited
only to its preferred embodiments, but is available for all that it discloses
and suggests to one of ordinary skill in the art. See Lamberti, 545 F.2d at
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750. Therefore, we are not persuaded by Appellant’s contention that
because
Kennedy teaches that copper is preferably administered as a
complex with the active ingredient . . . rather than administered
as a separate formulation, such as copper gluconate, . . . one of
ordinary skill in the art, starting with Kennedy, would not be
motivated to substitute the copper complex with a separate,
copper containing formulation, e.g., copper gluconate, such that
there would be no motivation, absent impermissible hindsight
bias, to combine Kennedy with any of Ferrara, Slaga, or
Bartunke.
(Appeal Br. 20; see also Reply Br. 4–5.)
“Attorney’s argument in a brief cannot take the place of evidence.” In
re Pearson, 494 F.2d 1399, 1405 (CCPA 1974). Therefore, we are not
persuaded by Appellant’s unsupported assertion that
although the remaining references teach the use of copper
gluconate in the treatment of cancer among other purposes,
starting with the teaching of Kennedy to mimic how copper (II)
behaves in the body in the presence of disulfiram after passage
through the stomach, one of ordinary skill in the art, and
especially in the medical arts, would not have a reasonable
expectation of success when selecting or substituting one
copper salt for another, absent the present teaching.
(Reply Br. 5.)
The rejection of claim 19 under 35 U.S.C. § 103(a) as unpatentable
over Kennedy, in combination with Ito or Lobler, and further in view of
Leishman, Ferrara, Slaga, and Bartunek, is affirmed. Claims 20 and 21 are
not separately argued and fall with claim 19.
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CONCLUSION
The preponderance of evidence relied upon by Examiner supports a
conclusion of obviousness.
In summary:
Claims
Rejected
Basis Affirmed Reversed
7, 9–12, 14, 15,
17–21
§ 103 Kennedy, Ito
or Lobler, Leishman
7, 9–12, 14,
15, 17–21

19, 20, 21 § 103 Kennedy, Ito
or Lobler, Leishman,
Ferrara, Slaga,
Bartunek
19, 20, 21
Overall Outcome 7, 9–12, 14,
15, 17–21

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