Ex Parte Dennis et al

Patent Trial and Appeal Board

Mar 8, 2017

12446836 (P.T.A.B. Mar. 8, 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.
12/446,836 04/23/2009 James E. Dennis CWR-7701US PCT 9507
68705 7590 03/10/2017
TAROLLI, SUNDHEIM, COVELL & TUMMINO, LLP
1300 EAST NINTH STREET
SUITE 1700
CLEVELAND, OH 44114
EXAMINER
POPA, ILEANA
ART UNIT PAPER NUMBER
1633
NOTIFICATION DATE DELIVERY MODE
03/10/2017 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):
rkline @ tarolli. com
docketing@tarolli.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte JAMES E. DENNIS,
ARNOLD I. CAPLAN, and DAVID J. FINK
Appeal 2016-002599
Application 12/446,836
Technology Center 1600
Before JEFFREY N. FREDMAN, ULRIKE W. JENKS, and
JOHN G. NEW, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal1 under 35 U.S.C. § 134(a) involving claims to a cell
delivery composition. The Examiner rejected the claims as obvious. We
have jurisdiction under 35 U.S.C. § 6(b). We affirm.
Statement of the Case
Background
“Promises of cures of a wide variety of diseases or tissue injuries by
specific replacement of damaged or diseased tissues by use of totipotent,
pluripotent or multi potent stem cells is on the horizon in clinical practice”
1 Appellants identify the Real Party in Interest as Rigel Pharmaceuticals, Inc.
(see App. Br. 2).
Appeal 2016-002599
Application 12/466,697
(Spec. 12). “One of the comerstones/obstacles in implementing this
technology is being able to direct the cells or tissue, engineered in vitro, to
the precise in vivo site were repair as needed.” (Spec. 13).
The Claims
Claims 1—3, 6—20, and 22—30 are on appeal. Claim 1 is representative
and reads as follows:
1. A cell delivery composition comprising:
a progenitor cell; and
a targeting moiety that binds to a target tissue,
wherein said targeting moiety selectively directs the
progenitor cell to the target tissue, wherein said targeting
moiety is modified with a lipophilic moiety, and wherein a
spacer moiety is inserted between the targeting moiety and the
lipophilic moiety.
The issues
A. The Examiner rejected claims 1—3, 6—20, 22—26, and 30 under
35 U.S.C. § 103(a) as obvious over Caplan2 and Ruoslahti3 (Final Act. 3—4).
B. The Examiner rejected claims 1—3, 6—20, and 22—30 under 35 U.S.C.
§ 103(a) as obvious over Caplan, Ruoslahti, Vellinga,4 and Kondo5 (Final
Act. 5—8).
2 Caplan et al., WO 2004/084950 A2, published Oct. 7, 2004 (“Caplan”).
3 Ruoslahti et al., US 2003/0045476 Al, published Mar. 6, 2003
(“Ruoslahti”).
4 Vellinga et al., Spacers Increase the Accessibility of Peptide. Ligands
Linked to the Carboxyl Terminus of Adenovirus Minor Capsid Protein IX, 78
J. Virology 3470-9 (2004) (“Vellinga”).
5 Kondo et al., Highly efficient delivery ofpi 6 antitumor peptide into
aggressive leukemia/lymphoma cells using a novel transporter system, 3
Molecular Cancer Therapeutics 1623—30 (2004) (“Kondo”).
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Appeal 2016-002599
Application 12/466,697
Because both rejections turn on the same issues and Appellants do not
separately argue any of the dependent claims, we will consider the rejections
together, and we select claim 1 as representative.
The issue with respect to these rejection is: Does the evidence of
record support the Examiner’s conclusion that Caplan and Ruoslahti render a
spacer moiety obvious in a cell delivery composition?
Findings of Fact
1. Claim 1 of Caplan is reproduced below:
A cell delivery composition comprising:
a) a progenitor cell; and
b) a targeting moiety that binds to a target tissue,
wherein said targeting moiety selectively directs the
progenitor cell to the target tissue.
(Caplan 45).
2. Caplan teaches
methods of delivering a progenitor cell to a target tissue in a
subject. . . . comprising: a) coating a progenitor cell with a
linker; b) contacting the coated progenitor cell with a targeting
moiety that binds to the linker and can then bind to the target
tissue; and c) administering the progenitor cell complexed with
the targeting moiety to a subject.
(Caplan 2:7-11).
3. Caplan teaches in “certain embodiments, the progenitor cell is
pre-coated with a linker, such as a protein G or protein A. Optionally, the
linker is modified with a lipophilic moiety” (Caplan 2:25—27).
4. Caplan teaches the “targeting moiety is a fusion protein . . . [an]
exemplary fusion protein comprises both an Fc fragment and a homing
peptide” (Caplan 4:3—6).
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Application 12/466,697
5. Caplan teaches “to include a spacer (such as a polypeptide
sequence or a chemical moiety) between a targeting moiety of the invention
and the tag in order to facilitate construction or to optimize its structural
constraints” (Caplan 25:22—25).
6. Ruoslahti teaches “a conjugate of the invention contains a
homing peptide of the invention linked to a tag . . . If desired, an appropriate
spacer can be positioned between the peptide and the support such that the
ability of the heart homing peptide to interact with the target molecule is not
hindered” (Ruoslahti || 92—93).
7. Vellinga teaches “labeling efficiency improved with increasing
spacer length, suggesting that spacers lift and expose the ligand at the capsid
surface” (Vellinga, abstract).
8. Kondo teaches a “Gly-Pro-Gly spacer, which serves to augment
delivery of a cargo peptide” (Kondo, abstract).
Principles of Law
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
KSR Inti Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). “If a person of
ordinary skill can implement a predictable variation, § 103 likely bars its
patentability.” Id. at 417.
Analysis
We adopt the Examiner’s findings of fact and reasoning regarding the
scope and content of the prior art as our own (Final Act. 3—8; FF 1—8) and
agree that claims 1 and 30 are obvious over Caplan and Ruoslahti. We
address Appellants’ arguments below.
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Application 12/466,697
Appellants separately argue each of the references, contending that
Vellinga “does not teach or suggest that a-helical spacers can be used in a
cell delivery composition of any kind”; that Kondo “does not teach or
suggest that Gly-Pro-Gly spacers can be used in a cell delivery composition
of any kind”; that Caplan “provide no teaching that a spacer can be inserted
between the targeting moiety and the lipophilic moiety”; and that Ruoslahti
does “not teach that a composition including a mammalian cell linked to a
homing peptide modified with a lipophilic moiety, wherein a spacer moiety
is inserted between the targeting moiety and the lipophilic moiety could
selectively direct the cell to a target tissue” (App. Br. 8—12).
We do not find these arguments persuasive, because they fail to
address the teachings of the references in combination. “Non-obviousness
cannot be established by attacking references individually where the
rejection is based upon the teachings of a combination of references.” In re
Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986). A reference “must be
read, not in isolation, but for what it fairly teaches in combination with the
prior art as a whole.” Id.
Caplan teaches coating a progenitor cell with a linker that connects to
a targeting moiety (FF 2) where the targeting moiety may be modified with a
lipophilic moiety (FF 3). While Caplan does not specifically teach a spacer
between the targeting moiety and the lipophilic moiety, Caplan does teach
the use of spacers to separate the targeting moiety from tags to eliminate
structural constraints (FF 5). Ruoslahti teaches the use of spacers between
targeting moieties and tags to avoid hindering the ability of the targeting
moiety to interact with the target (FF 6).
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Application 12/466,697
We agree with the Examiner that the use of a spacer in Caplan’s
composition would have been obvious to the ordinary artisan because
“spacers were known and routinely used in the prior art to prevent steric
hindrance and provide optimum interaction between targeting moieties and
their targets” (Ans. 6).
Appellants contend
that one skilled in the art would not find it predictable and/or
had a reasonable expectation of success in view of Caplan et al.
and Ruoslahti et al. that a cell delivery composition, including a
progenitor cell and a targeting moiety modified with a
lipophilic moiety, wherein a spacer moiety is inserted between
the targeting moiety and the lipophilic moiety, would
selectively direct the progenitor cell to the target tissue.
(App. Br. 15). Appellants contend that Caplan does “not discuss the use of
spacers, let alone inserting a spacer between a lipophilic moiety and a
homing peptide” (App. Br. 17).
We are not persuaded because Caplan teaches “to include a spacer
(such as a polypeptide sequence or a chemical moiety) between a targeting
moiety of the invention and the tag in order to facilitate construction or to
optimize its structural constraints” (FF 5) and Ruoslahti teaches that spacers
ensure that the ability of a targeting “peptide to interact with the target
molecule is not hindered” (FF 6). Thus, an ordinary artisan would have had
a reasonable expectation of success because inclusion of a spacer between
the targeting and lipophilic moieties taught by Caplan (FF 2—3) would have
been expected to enhance the ability of the targeting moiety to interact with
the target. “Obviousness does not require absolute predictability of success
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Application 12/466,697
. . . all that is required is a reasonable expectation of success.'1'’'’ In re Kubin,
561 F.3d 1351, 1360 (Fed. Cir. 2009) (emphasis in original).
We recognize, but find unpersuasive, Appellants’ argument that
“Appellants] [are] under no obligation to submit evidence of
nonobviousness” because “the Office Action has failed to produce a prima
facie case of obviousness” (App. Br. 19). We find that the Examiner has
established a prima facie case of obviousness based on the teachings of
Caplan and Ruoslahti discussed already, including a reasonable expectation
of success given the teachings of both references to use a spacer (FF 5—6).
Not only do Appellants fail to provide any evidence rebutting the
Examiner’s position, Appellants fail to provide any reasoning or logic as to
why the ordinary artisan, motivated by Ruoslahti to use a spacer, would have
had any difficulty in inclusion of a spacer as taught by both Caplan and
Ruoslahti into a targeting peptide (FF 5—6).
Appellants contend, with regard to claim 30, that “an ordinary skilled
artisan would not modify the cell delivery composition of Caplan et al. by
using an Fc/targeting moiety fusion protein linked to the lipophilic moiety in
view of the teachings of Caplan” because “Caplan et al. does not teach or
suggest that an Fc domain itself can be used as a spacer of any kind” (App.
Br. 21).
We are not persuaded. Caplan specifically teaches that an “exemplary
fusion protein comprises both an Fc fragment and a homing peptide” (FF 4).
Because the homing peptide represents the targeting moiety in Caplan, the
Fc fragment is reasonably interpreted as functioning as a spacer in this
disclosure itself. Even if the Fc fragment, a polypeptide sequence, does not
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Application 12/466,697
function as a spacer in this embodiment, Caplan teaches the spacer may be a
polypeptide sequence (FF 5), rendering the use of the Fc fragment as a
spacer obvious.
Appellants contend that “using an Fc/targeting moiety fusion protein
further fused/linked to the lipophilic moiety would destroy the intent,
purpose, and/or function of an Fc domain tagged targeting moiety in a cell
delivery composition disclosed by Caplan” (App. Br. 22). Appellants
contend “that fusing an Fc domain to a lipophilic moiety and a targeting
moiety would significantly change the principle of operation of [an] Fc
domain tagged targeting moiety in a cell delivery composition disclosed by
Caplan” (App. Br. 23).
We do not find this argument persuasive and agree with the Examiner
that:
While it is true that the Fc fragment could be useful for
isolation and purification, isolation and purification necessarily
occur before attaching the lipophilic moiety. Thus, attaching
the lipophilic moiety to the C-terminus of the Fc fragment
cannot impede isolation and purification because attaching the
lipophilic moiety occurs after the isolation and purification
steps are completed.
(Ans. 12). We also agree with the Examiner’s finding that it would be
obvious to the skilled artisan to “attach a lipophilic moiety to the free C-
terminus of the Fc fragment for inserting the targeting moiety together with
the Fc spacer into the cell membrane such that the targeting moiety would be
exposed unencumbered on the cell surface and able of efficiently interacting
with its target tissue” (Ans. 11).
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Application 12/466,697
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that
Caplan and Ruoslahti render a spacer moiety obvious in a cell delivery
composition.
SUMMARY
In summary, we affirm the rejection of claims 1 and 30 under
35 U.S.C. § 103(a) as obvious over Caplan and Ruoslahti. Claims 2, 3, 6—
20, and 22—26 fall with claims 1 and 30.
We affirm the rejection of claims 1 and 30 under 35 U.S.C. § 103(a)
as obvious over Caplan, Ruoslahti, Vellinga, and Kondo. Claims 2, 3, 6—20,
and 22—29 fall with claims 1 and 30.
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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