Ex Parte Caplan et al

Patent Trial and Appeal Board

Jul 6, 2017

10550590 (P.T.A.B. Jul. 6, 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
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APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
10/550,590 06/01/2006 Arnold Caplan CWR-7781PCT/US 1634
68705 7590 07/10/2017
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
07/10/2017 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 ARNOLD I. CAPLAN and JAMES E. DENNIS
Appeal 2015-003611
Application 10/550,5901
Technology Center 1600
Before DONALD E. ADAMS, RICHARD M. LEBOVITZ, and
JEFFREY N. FREDMAN, Administrative Patent Judges.
ADAMS, Administrative Patent Judge.
DECISION ON APPEAL
This appeal under 35 U.S.C. § 134(a) involves claims 1, 2, 4, 6, 8, 9,
11, 13-15, 26, 29, 39, 41, 45, 47, 48, 50, 52, 54—56, 67, 70, 80, 82, 85, 190,
and 191 (App. Br. 2).2 Examiner entered a rejection under 35 U.S.C.
§ 103(a). We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
1 Appellants identify the real party in interest as “Case Western Reserve
University” (App. Br. 2).
2 Pending “[cjlaims 3, 16-18, 20-25, 32-38, 46, 57-59, 61-66, 73-79, 84, 86-
89, 96-97, 99, 101, 103-105, 107, 109-110, 112, 114-119, 121-127, 130,
133-140, 142-143, 145, 147-149, 151, 153-154, 156, 158-163, 165-171, 174,
177-184, 186, [and] 188-189[] [stand] withdrawn” from consideration (App.
Br. 2).
Appeal 2015-003611
Application 10/550,590
STATEMENT OF THE CASE
Appellants disclose “compositions and methods for delivering
progenitor cells to target tissues” (Spec. 2). Claim 1 is representative and
reproduced below:
1. A composition for targeting a progenitor cell to a target
tissue 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 progenitor cell
is linked to said targeting moiety, wherein said targeting moiety
is modified with a lipophilic moiety or said progenitor cell is
pre-coated with a linker, and wherein said linked targeting
moiety enhances adherence of the progenitor cell to the target
tissue when administered to a target tissue injury site and
wherein the targeting moiety does not adversely affect
progenitor cell viability, mitotic potential, and phenotype.
(App. Br. 32.)
2
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Application 10/550,590
The claims stand rejected as follows:
Claims 1, 2, 4, 6, 8, 9, 11, 13-15, 26, 29, 39, 41, 45, 47, 48, 50, 52,
54—56, 67, 70, 80, 82, 85, 190, and 191 stand rejected under 35 U.S.C.
§ 103(a) as unpatentable over the combination of Logtenberg,3 Caplan,4
Colsky,5 Kim,6 Thomas,7 and Simmons.8
ISSUE
Does the preponderance of evidence relied upon by Examiner support
a conclusion of obviousness?
3 Logtenberg et al, WO 00/23570 Al, published Apr. 27, 2000.
4 Arnold I. Caplan and Scott P. Bruder, Mesenchymal stem cells: building
blocks for molecular medicine in the 21st century, 7 TRENDS IN
Molecular Medicine 259-264 (2001).
5 Arthur S. Colsky and James S. Peacock, Palmitate-derivatized antibodies
can function as surrogate receptors for mediating specific cell-cell
interactions, 124 Journal of Immunological Methods 179-187 (1989).
6 Stanley A. Kim and James S. Peacock, The use of palmitate-conjugated
protein A for coating cells with artificial receptors which facilitate
intercellular interactions, 158 Journal of Immunological Methods 57—
65 (1993).
7 J Terrig Thomas et al., Cartilage collagens: strategies for the study of
their organisation and expression in the extracellular matrix, 53 Annals of
the Rheumatic Diseases 488-496 (1994).
8 Paul J. Simmons et al., Isolation, Characterization and Functional Activity
of Human Marrow Stromal Progenitors in Hemopotesis, Advances in Bone
Marrow Purging and Processing: Fourth International Symposium 271—280
(1994).
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Application 10/550,590
FACTUAL FINDINGS (FF)
FF 1. Logtenberg discloses, inter alia, a method of inserting lipid-modified
proteinaceous molecules into the membrane of a cell (Logtenberg 3: 23—29;
Ans. 3).
FF 2. Logtenberg discloses that its method “appears to be generally
applicable to all cell types” (Logtenberg 5: 19-20; see also id. at 12: 11
(Logtenberg’s “cell may be any type of prokaryotic or eukaryotic cell”);
Ans. 3).
FF 3. Logtenberg discloses that “[o]ne of the most prominent applications
of [its method] lies in the field of cell therapy as a strategy for the treatment
of human diseases” (Logtenberg 4: 29—31; see also id. at 2: 24—25 (“Cell
therapy is a strategy for the treatment of many diseases. The aim of cell
therapy is to replace or repair damaged tissue or organs or to enhance the
biological function of cells”); Ans. 3).
FF 4. Logtenberg’s method provides recipient cells with, inter alia, the
ability to recognize a target (Logtenberg 4: 7—11; Ans. 3).
FF 5. Logtenberg’s proteinaceous molecules may be “receptors, co­
receptors, (membrane-bound) ligands,” “single chain variable fragments
(scFv),” or “antibodies, fragments derived from antibodies such as fragment
antigen binding (FAB) fragments” (Logtenberg 8: 30—32 and 9: 7 and 25—
26; Ans. 3).
FF 6. Logtenberg discloses:
In a preferred embodiment [the] lipid-modified proteinaceous
molecules provide the particles with membranes derived from
cells with a new target cell specificity. Such specificity may be
added through, for example, a scFv molecule with a specificity
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Application 10/550,590
for an antigen on the surface of a cell type previously not
belonging to the target cell pool of said particle.
(Logtenberg 14: 8—14; Ans. 3.)
FF 7. Logtenberg’s method
allows [for] the rapid and efficient insertion of lipid-tagged
(LT) proteins into the membrane of prokaryotic and eukaryotic
cells. The procedure appears to be applicable to most
eukaryotic cell types including freshly isolated cell populations.
LT-scFv antibody fragments inserted into cell membranes
where shown to remain fully functional, capable of binding
soluble and membrane-bound molecules expressed by other
cells.
(Logtenberg 15: 31—16: 4; see generally id. at 24—25; Ans. 4.)
FF 8. Logtenberg discloses that “[t]he insertion of LT-scFv’s [into cells]
did not affect cell proliferation [], nor cell viability” (Logtenberg 34: 8—10;
4; see generally id. at 39: 13—20; see also Ans. 3—4).
FF 9. Examiner finds that while Logtenberg discloses “tissue repair, [it
does] not specifically teach injecting the cell directly into the tissues such as
cartilage or bone, nor do they teach [] a mesenchymal stem cell (MSC)”
(Ans. 4).
FF 10. Caplan discloses that “the multi-lineage potential of MSCs, their
exquisite sensitivity to specific signaling molecules, and their relative ease
of handling in vitro, they are a potentially powerful tool in tissue
engineering. This approach has been employed, using animal models, for
bone[ ], cartilage[ ], tendon[ ], marrow stroma[ ] and muscle[ ] repair and
regeneration” (Caplan 261 (endnotes omitted); Ans. 4).
FF 11. Caplan discloses that “[b]oth animal and human MSCs in culture
have been successfully transduced with exogenous genes using several
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different vectors without an apparent defect of their stem cell properties[ ]”
(Caplan 261 (endnotes omitted); Ans. 4).
FF 12. Caplan discloses that
MSCs could be injected into diarthrodial joint spaces to
contribute to repair or regeneration of meniscal or articular
cartilage[ ] Methods to stimulate expression of specific cell
surface ligands, either natural or engineered, that can mediate
selective attachment to known receptors in target tissues of
interest will be of considerable clinical benefit.
(Caplan 262 (endnotes omitted); see id. (“targeting the infused cells to
specific tissue locations could have a large impact on future therapeutic uses
of MSCs for other diseases”); Ans. 4.)
FF 13. Examiner finds that “[ajlthough [the combination of] Logtenberg []
and Caplan [] teach coating their cells with lipid-modified antibodies, they
do not specifically teach palmitoylated antibodies or attaching the antibody
via a palmitoylated protein A linker” and relies on Colsky and Kim to make
up for this deficiency in the combination of Logtenberg and Caplan (Ans. 5).
FF 14. Colsky discloses “a method for incorporating palmitate-derivatized
antibody molecules onto cell membranes where they function as [‘Jsurrogate
receptors’ (SR) for mediating specific cellular interactions” and, thereby,
enable the palmitate-derivatized antibody molecules “to cooperate with
endogenous target recognition structures in receptor-ligand interactions at
the cell-cell interface” (Colsky, Abstract; see id. at 180; Ans. 5).
FF 15. Kim discloses “[a] method [] in which palmitate-conjugated protein
A (pal-protein A) incorporated onto cell membranes is used to anchor
antibodies on the surface of cells,” wherein “cells can be coated with
antibody (Ab) molecules of a desired specificity that can serve as artificial
receptors for soluble or cell surface antigens (Ags)” (Kim, Abstract; see id.
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at 58 (“The increased avidity supplied by [Kim’s] artificial receptors
mediated a high level of heterotypic cell-cell conjugation. The method
presented here should be broadly applicable to many studies where it is
desired to target specific molecules to cell surfaces or to induce specific
intercellular interactions”); Ans. 5).
FF 16. Examiner finds that “[although [the combination of] Logtenberg [],
Caplan [,] Colsky [], and Kim teach specific delivery to cartilage by using
antibody-coated MSCs, they do not specifically teach using anti-collagen II
antibodies []” and relies on Thomas to disclose “that collagen II is a
cartilage-specific collagen” (Ans. 5, citing Thomas 488).
FF 17. Examiner relies on Simmons to disclose the marker “Stro-1,” which
is expressed on MSCs (Ans. 4, citing Simmons 273).
FF 18. Beauchamp discloses “that the majority of transplanted muscle
precursor cells [] die in host muscle and only a minority (less than 1 %) are
responsible for new muscle formation” (App. Br. 21, citing Beauchamp9
1115).
ANALYSIS
Based on the combination of Logtenberg, Caplan, Colsky, Kim,
Thomas, and Simmons, Examiner concludes that, at the time Appellants’
invention was made, it would have been prima facie “obvious to use the
method of Logtenberg [] with modified MSCs [the “progenitor cell” of claim
1 modified with the antibodies or protein serving as the recited “targeting
moiety”] and administer the modified MSCs directly into the damaged bone
9 Jonathan R. Beauchamp et al., Dynamics of Myoblast Transplantation
Reveal a Discrete Minority of Precursors with Stem Cell—like Properties as
the Myogenic Source, 144 Journal of Cell Biology 1113-1121 (1999).
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or cartilage to achieve the predictable result of specifically targeting the cells
to the damaged cartilage or bone with the purpose of regenerating the
damaged cartilage or bone” (Ans. 4). In this regard, Examiner concludes:
It would have been obvious to one of skill in the art, at the time
the invention was made, to modify the composition of
Logtenberg [] and Caplan [] by using palmitoylated antibodies
or a palmitoylated protein A linker to achieve the predictable
result of coating the cells with antibodies as targeting agents.
(Ans. 5.) Examiner further concludes:
[I]t would have been obvious to one of skill in the art, at the
time the invention was made, to use an anti-collagen II antibody
in the method [suggested by the combination of Logtenberg,
Caplan, Colsky, and Kim] to achieve the predictable result of
targeting their MSCs to the cartilage tissue.
(Ans. 5—6.)
We are not persuaded by Appellants contention that Logtenberg:
[Does] not disclose a proteinaceous molecule (e.g., an antibody)
can be used to target the cell or lymphocyte to a site of injury
when administered to a site of injury, let alone enhance
adherence of the progenitor cell to the target tissue while not
adversely affecting progenitor cell viability, mitotic potential,
and phenotype.
(App. Br. 13).
Logtenberg discloses a method of inserting lipid-modified
proteinaceous molecules, such as lipid-modified antibodies or antibody
fragments, into the membrane of a cell, wherein the method is “generally
applicable to all cell types” (LL 1, 2, and 5—8). In this regard, Logtenberg
discloses that the insertion of lipid-modified antibodies into the membrane
of cells provides the modified cells with the ability to specifically bind target
cells (LL 6 and 7), the same purpose of the “targeting moiety” of claim 1.
Logtenberg further discloses that “[t]he insertion of LT-scLv’s [into cells]
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Application 10/550,590
did not affect cell proliferation [], nor cell viability” (FF 8). In addition,
Caplan discloses that MSCs are relatively easy to handle and may be
manipulated “without an apparent defect of their stem cell properties” (FF
10—11 (endnote omitted)). Colsky and Kim further support Examiner’s
finding that the modification of a cell with an antibody, according to the
combination of Logtenberg, Caplan, Colsky, Kim, and Thomas is broadly
applicable and provides a mechanism to specifically target cells to a desired
location, such as cartilage (FF 14—16). Therefore, we are not persuaded by
Appellants contention “that without the experimental data disclosed in
the[ir] [Specification, one having skill in the art could not have found it
predictable that attaching proteinaceous molecules to progenitor cells as
recited in claim 1 would not adversely affect progenitor cell viability,
mitotic potential, and phenotype of the progenitor cells []” (App. Br. 22,
citing Specification 39: 23—28; 43: 8—9, 13—14, and 17—25; and Figs. 2—4).
In re O’Farrell, 853 F.2d 894, 903—904 (Fed. Cir. 1988) (“Obviousness does
not require absolute predictability of success ... all that is required is a
reasonable expectation of success”).
A reference disclosure is available for all that it discloses and suggests
to one of ordinary skill in the art. In re Lamberti, 545 F.2d 747, 750 (CCPA
1976). Therefore, for the foregoing reasons, we are not persuaded by
Appellants’ contentions regarding “homing” or the difference between
lymphocytes and progenitor cells (App. Br. 13—15 and 22—24; see also id. at
17-20; Reply Br. 3-4).
For the foregoing reasons, we are not persuaded by Appellants’
contention that the combination of Logtenberg, Caplan, Colsky, Kim, and
Thomas fails to provide a person of ordinary skill in this art with a
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reasonable expectation of successfully preparing a composition comprising a
progenitor cell and a targeting moiety, within the scope of Appellants’
claimed invention, wherein “a proteinaceous molecule linked to a progenitor
cell could enhance adherence of a progenitor cell to a target tissue site when
administered to a target tissue injury site and not adversely affect progenitor
cell viability, mitotic potential, and phenotype” (App. Br. 15; see also id. at
16 (Caplan alone, does not suggest: “a means for increasing the efficiency
of mesenchymal stem cell engraftment;” “a composition having a progenitor
cell linked to a targeting moiety, modified with a lipophilic moiety, capable
of targeting target tissue at a target tissue injury site;” or “that such
compositions would not adversely affect progenitor cell viability, mitotic
potential, and phenotype of a progenitor cell”); id. at 24; Reply Br. 2 and 3—
4; cf. FF 1—16; Ans. 4—6). In re O’Farrell, 853 F.2d at 903.
For the foregoing reasons, we are not persuaded by Appellants’
contention that the combination of Logtenberg, Caplan, Colsky, Kim, and
Thomas fails to
suggest attaching a targeting moiety onto the surface of a cell to
enhance adherence of the cell to tissue in which the cells are
administered to, let alone linking a targeting moiety to a
progenitor cell to target the progenitor cell to target tissue at a
target tissue injury site and not adversely affect progenitor cell
viability, mitotic potential, and phenotype
(App. Br. 15; see also id. at 15—16 and 20-21; Reply Br. 2; cf. FF 1—16; see
generally FF 14 (Colsky discloses “a method for incorporating palmitate-
derivatized antibody molecules onto cell membranes where they function as
[‘jsurrogate receptors’ (SR) for mediating specific cellular interactions” and,
thereby, enable the palmitate-derivatized antibody molecules “to cooperate
with endogenous target recognition structures in receptor-ligand interactions
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Application 10/550,590
at the cell-cell interface”); FF 15 (Kim discloses a broadly applicable
“method [] in which palmitate-conjugated protein A (pal-protein A)
incorporated onto cell membranes is used to anchor antibodies on the surface
of cells,” wherein “cells can be coated with antibody (Ab) molecules of a
desired specificity that can serve as artificial receptors for soluble or cell
surface antigens (Ags)” (FF 15).
As discussed above, the combination of Logtenberg, Caplan, Colsky,
Kim, and Thomas suggests a composition, within the scope of Appellants’
claimed invention, comprising a progenitor cell and a targeting moiety, such
as an antibody to type II collagen (FF 1—16). Therefore, we are not
persuaded by Appellants’ contention that Thomas, alone, fails to “teach that
antibodies to type II collagen can be linked to progenitor cells and once
linked used to enhance adherence of the progenitor cell to a target tissue
injury site (App. Br. 17; see generally Reply Br. 2)
Appellants’ claimed invention does not require any particular
percentage of targeting moiety modified precursor cells to survive
implantation or be responsible for the formation of new tissue (see App. Br.
32) as long as some are effective to achieve tissue targeting. Therefore, we
are not persuaded by Appellants’ reliance on Beauchamp’s disclosure of the
percentage of unmodified muscle precursor cells that survive implantation
and form new muscle (App. Br. 21—22; see Reply Br. 4—5). Further, for the
reasons set forth above, we are not persuaded by Appellants’ contention that
in view of Beauchamp and without the evidence provided by their
Specification, “one having skill in th[is] art could not have found it
predictable that attaching proteinaceous molecules to progenitor cells as
recited in claim 1 would not adversely affect progenitor cell viability,
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Application 10/550,590
mitotic potential, and phenotype of the progenitor cells” (App. Br. 22; cf. FF
1-16; Ans. 4-6).
For the foregoing reasons, we are not persuaded by Appellants’
contention that the rejection on this record: fails to provide “anyone having
skill in the relevant art [with] a reasonable expectation of success,” “is too
general and lacking in the type of particularity that is required to make out a
prima facie case of obviousness,” is conclusory, and based in hindsight
(App. Br. 24—27; see Reply Br. 2). “The combination of familiar elements
according to known methods is likely to be obvious when it does no more
than yield predictable results.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398,
416 (2007). Further, notwithstanding Appellants’ contention to the contrary:
“[A]ny need or problem known in the field of endeavor at the time of
invention and addressed by the patent can provide a reason for combining
the elements in the manner claimed.” KSR, 550 U.S. at 420. Therefore,
notwithstanding Appellants’ contention to the contrary, Examiner
established an evidentiary basis on this record to support a conclusion that
the combination of Logtenberg, Caplan, Colsky, Kim, and Thomas suggests
a composition comprising a progenitor cell and a targeting moiety, within
the scope of Appellants’ claimed invention and a reason for making such a
composition (FF 1—16; see Ans. 4—6).
CONCLUSION OF LAW
The preponderance of evidence relied upon by Examiner supports a
conclusion of obviousness. The rejection of claim 1 under 35 U.S.C.
§ 103(a) as unpatentable over the combination of Logtenberg, Caplan,
Colsky, Kim, Thomas, and Simmons is affirmed. Claims 2, 4, 6, 8, 9, 11,
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13-15, 26, 29, 39, 41, 45, 47, 48, 50, 52, 54—56, 67, 70, 80, 82, 85, 190, and
191 are not separately argued and fall with claim 1.
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
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