Ex Parte ALLEN

Patent Trials and Appeals Board

May 2, 2019

14775032 - (D) (P.T.A.B. May. 2, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
14/775,032 09/11/2015
22045 7590 05/06/2019
Brooks Kushman
1000 Town Center
22nd Floor
SOUTHFIELD, MI 48075
FIRST NAMED INVENTOR
Matthew J. ALLEN
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.
WSU 0230 PUSA 3948
EXAMINER
DICKINSON,PAUL W
ART UNIT PAPER NUMBER
1618
NOTIFICATION DATE DELIVERY MODE
05/06/2019 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):
docketing@brookskushman.com
kdilucia@brookskushman.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MATTHEW J. ALLEN
Appeal2018-005809
Application 14/775,032 1
Technology Center 1600
Before DEMETRA J. MILLS, RICHARD M. LEBOVITZ, and
DAVID COTTA, Administrative Patent Judges.
LEBOVITZ, Administrative Patent Judge.
DECISION ON APPEAL
The claims in this appeal are directed to a liposome comprising a
europium metal complex. The Examiner rejected the claims under 35
U.S.C. § 103 as obvious. Pursuant to 35 U.S.C. § 134, Appellant appeals the
Examiner's determination that the claims are unpatentable. We have
jurisdiction for the appeal under 35 U.S.C. § 6(b ). The Examiner's decision
is affirmed.
STATEMENT OF THE CASE
The claims stand rejected by the Examiner as follows:
Claims 1-3, 5-12, 14, and 15 under pre-AIA 35 U.S.C. § 103(a) as
obvious in view of Allen et al. (WO 2011/090977 Al, published July 28,
1 The Appeal Brief ("Appeal Br." entered Dec. 4, 2017) lists Wayne State
University as the real party in interest. Appeal Br. 2.
Appeal2018-005809
Application 14/775,032
2011) ("Allen") and Port (US 2007/0292354 Al, published Dec. 20, 2007).
Ans. 3.
Claims 1-12, 14, and 15 under pre-AIA 35 U.S.C. § I03(a) as obvious
in view of Allen, Port, and Peterson et al. (US 2012/0213698 Al, Aug. 23,
2012) ("Peterson"). Ans. 4.
Appellant addressed the rejections together, and only argued the
patentability of independent claim 1. Separate arguments for the
patentability of the dependent claims were not provided. Therefore, all the
claims stand or fall with claim 1. 37 C.F.R. § 4I.37(c)(l)(iv).
Independent claim 1 is reproduced below:
1. A composition comprising:
a liposome;
a europium metal complex disposed within the liposome,
the europium metal complex including a europium metal ion
and a multi-dentate ligand selected from the group consisting of
cryptands and thiacryptands, the europium metal complex
including Eu2+, and
if necessary, counter-ions to maintain charge neutrality,
the europium metal ion being switchable from a 2+ oxidation
state to a 3+ oxidation state when encapsulated in the liposome.
DISCUSSION
The Examiner found that Allen describes a europium metal complex
comprising a multi-dentate ligand which meets all the limitations of claim 1.
Compare Allen, Abstract, Compound "1" to appealed claim 15, where Y 1
and Y2 are oxygen. Ans. 3. The Examiner also found that Allen describes
that the complex is useful for medical diagnostic applications, including as a
contrast agent for magnetic resonance imaging (MRI). Id. The Examiner
found that Allen does not disclose incorporation of its europium metal
complex into a liposome as required by the claim. Id. To meet this
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Application 14/775,032
deficiency, the Examiner cited Port as disclosing europium contrast agents
incorporated into liposomes. Id. The Examiner determined it would have
been obvious to one of ordinary skill in the art to encapsulate Allen's
complex into a liposome as taught by Port to facilitate its use as an MRI
contrast agent. Ans. 4. The Examiner further cited Peterson to meet the
limitations in dependent claims that the specifically recited phospholipids
are present in the liposomes. Id.
Appellant contends that the "present invention is particularly
surprising since Allen states that Eu2+ [ also known as Eu(II)] compounds are
'the most oxidatively stable aqueous Eu(II) complexes known to date"' and
thus it would not have been expected that "the europium metal ion" is
"switchable from a 2+ oxidation state to a 3+ oxidation state when
encapsulated in the liposome" as required by the claim. Appeal Br. 3.
This argument is not persuasive. As discussed by Appellant, Allen
teaches that its invention "provides a method for forming the most
oxidatively stable aqueous Eu(II) complexes known to date." Allen 4:3--4.
This statement, however, does establish that all of Allen's europium metal
complexes are exclusively in the Eu(II) state. Allen further teaches: "A
strategy for favoring Eu(II) [Eu2+] over Eu(III) [Eu3+] in aqueous solution
involves the synthesis and use of ligands that would preferentially
coordinate to large, soft, electron rich metals like Eu(II)." Allen 4:4---6
( emphasis added). Allen explains how a ligand ("cryptand") can be
gradually chemically modified to accomplish several goals, including "to
favor the electron rich Eu(II) over Eu(III)." Allen 4:7-5:3. It is apparent
from these teachings that the ligands described in Allen can have a varying
ability to coordinate and favor the Eu(II) form over the Eu(III) form.
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Application 14/775,032
Accordingly, one skilled in the art reading Allen would have understood that
a complex comprising the metal Eu may not be completely in the Eu(II)
form, and may include complexes having the Eu(III) form, as well, because
the ligands "preferentially coordinate" the europium in the + 2 oxidative
form, but not necessary exclusively. Consistently, Allen teaches that
cryptand 2 has "increased oxidative stability" over cryptand 1 when
complexed to europium, indicating that the cryptand 1 ligand is less stable
and may experience some degree of oxidation and therefore would
reasonably be considered "switchable" between oxidative states Eu(II) and
Eu(III) as required by rejected claim 1. Allen 9: 14--16; Fig. 1 showing
cryptands 1 and 2.
Appellant did not provide evidence that the ligand cited in Allen by
the Examiner (Final Act. 3 2) is one in which no Eu(III) is coordinated and in
which Eu(II), when coordinated by the ligand, would not be switchable to
the Eu(III) form. The claims do not require that the europium metal ion be
switchable between oxidation forms to any specific degree.
Appellant also argues, citing disclosure in the Specification, that
"combination [ ofJ Allen and Port does not predict that an Eu2+ complex
would be switchable when encapsulated in a liposome or that the Eu2+ would
remain unoxidized until it reaches a target tissue." Appeal Br. 3. Appellant
contends this property is "surprising." Id.
This argument is not supported by adequate objective evidence. The
rejection is based on the obviousness of encapsulating Allen's europium
complex comprising a multi-dentate ligand in a liposome as described by
2 Compare the ligand recited in claim 1 to the ligand 1 in Figure 1 of Allen.
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Application 14/775,032
Port. Appellant did not dispute that Allen's complex is the same complex
which is claimed. Appellant also did not dispute the Examiner's reasoning
as to why it would have been obvious to incorporate Allen's europium metal
complex into a liposome of Port.
Appellant has not provided persuasive evidence that the property
relied upon to establish the asserted "surprising" and "unexpected" result
(Appeal Br. 3; Reply Br. 1-2) is a property of the europium metal complex
in a liposome, rather than a property of the complex, itself. This distinction
is important because if the "switchable" capability of the europium complex
is of the complex, itself, then it is insufficient to overcome the rejection
because an unappreciated property of a known compound does not confer
patentability on it.
1991):
As stated in In re Baxter Travenol Labs., 952 F.2d 388, 392 (Fed. Cir.
Baxter argues that the unexpected hemolysis-suppression
quality of DEHP rebuts any prima facie showing of
obviousness. However, when unexpected results are used as
evidence of nonobviousness, the results must be shown to be
unexpected compared with the closest prior art. In re De
Blauwe, 736 F.2d 699, 705 (Fed.Cir.1984). Here, the closest
prior art was the Becker system, utilizing a DEHP primary bag.
Mere recognition of latent properties in the prior art does not
render nonobvious an otherwise known invention. In re
Prindle, 297 F.2d 251,254 (CCPA 1962). Since the prior art
bags plasticized with DEHP were inherently suppressing
hemolysis, albeit unknown at the time of the Becker document,
this hemolysis-suppressing function is not a basis for rebutting
a prima facie finding of obviousness.
In the same way, if the switchable capability of Allen's europium
metal complex is a property of the complex, alone, it is not a basis for
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Application 14/775,032
rebutting a prima facie finding of obviousness because such property is
inherent to the europium metal complex described by Allen.
Appellant argues that Allen teaches that the Eu(II) complex is stable
and it would not be obvious that "the liposome encapsulated Eu2+ complex
would be switchable from the 2+ to 3+ oxidation states given the oxidative
stablility [ sic, stability] of these types of compounds in water." Appeal Br.
5.
Appellant has not demonstrated that the claimed complex acts any
differently in water or in an aqueous solution than how it behaves in a
liposome. The Specification discloses:
Surprisingly, the europium metal ions are switchable between a
2 + and 3 + oxidation state even when encapsulated in the
liposome as illustrated in Figure 1. The oxidation of Eu2+ to
Eu3+ provides orthogonal modes of detection by MRI.
Spec. ,r 32.
The Specification does not disclose that the switch between the 2+
(Eu(II)) and 3+ (Eu(III)) oxidation states does not occur in water, but only
occurs in liposomes. Rather, the Specification states the switch occurs "even
when encapsulated in the liposome," implying that it also occurs when
present in water or in another aqueous solution, 3 and is no different when
present in a liposome. Appellant does not identify, and we do not find, a
difference in the oxidative behavior of the europium metal complex in a
liposome as compared to the europium complex, alone, as described in
Allen. Nor does Appellant direct us to evidence to support that the ordinary
3 The Allen publication is authored by the same inventor as the inventor of
the instant Application and describes the behavior of europium complexes in
water. Allen 8:25-28.
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artisan would have expected that incorporating the europium complex into
liposome would change the properties of the europium complex, i.e., that it
would lose the ability to switch oxidative states.
A case of prima facie obviousness can be rebutted with a showing of
unexpected results. In re Soni, 54 F.3d 746, 750 (Fed. Cir. 1995). Those
results must be "surprising or unexpected" to one of ordinary skill in the art
when considered in the context of the prior art. Id.; Iron Grip Barbell Co.,
Inc. v. USA Sports, Inc., 392 F.3d 1317, 1323 (Fed. Cir. 2004). Under Soni,
"the PTO must consider comparative data in the specification in determining
whether the claimed invention provides unexpected results." Soni, 54 F.3d
at 750. "Mere lawyer's arguments and conclusory statements in the
specification, unsupported by objective evidence, are insufficient to establish
unexpected results." In re Wood, 582 F.2d 638, 642 (CCPA 1978). See also
CFMT, Inc. v. Yieldup Int'! Corp., 349 F.3d 1333, 1342 (Fed. Cir. 2003).
In this case, Appellant has not provided persuasive evidence to
establish that the ability to switch between oxidative states in liposomes was
unexpected. The Specification discloses that the ability to switch oxidative
states is useful when using liposomes comprising the claimed europium
metal complex. Spec. ,r 45. However, Appellant did not establish by
objective evidence in this Appeal that the ability of the claimed europium
metal complex to switch oxidative states in the liposome was unexpected in
view of the teachings in Allen, as discussed above, that certain of its ligands
(when in water) favor coordinating Eu(II), but are not excluded from also
being present in the Eu(III) form.
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Application 14/775,032
For the foregoing reasons, the obviousness rejections of claim 1 is
affirmed. Claims 2-12, 14, and 15 were not argued separately and thus fall
with claim 1.
TIME PERIOD
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(l )(iv).
AFFIRMED
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