Ex Parte Askari et al

Patent Trial and Appeal Board

Feb 10, 2017

14213520 (P.T.A.B. Feb. 10, 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.
14/213,520 03/14/2014 Syed H. ASKARI 40049-707.201 1078
21971 7590 02/14/2017
WILSON, SONSINI, GOODRICH & ROSATI
650 PAGE MILL ROAD
PALO ALTO, CA 94304-1050
EXAMINER
PARAD, DENNIS J
ART UNIT PAPER NUMBER
1612
NOTIFICATION DATE DELIVERY MODE
02/14/2017 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
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte SYED H. ASKARI and GEORGE HORNG
Appeal 2016-001937
Application 14/213,520
Technology Center 1600
Before JEFFREY N. FREDMAN, JOHN E. SCHNEIDER and
TIMOTHY G. MAJORS, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal1 under 35U.S.C. § 134 involving claims to a fully
synthetic, polyglycol-based biocompatible hydrogel polymer matrix. The
Examiner rejected the claims as obvious. We have jurisdiction under 35
U.S.C. § 6(b). We affirm.
Statement of the Case
Background
“During and after administration of a cell based therapy to a target
site, the therapeutic cells may not be sufficiently protected. Cells which are
not protected may undergo apoptosis, necrosis, hypertrophy, or senescence;
1 Appellants identify the Real Party in Interest as Medicus Biosciences LLC
(see App. Br. 3).
Appeal 2016-001937
Application 14/213,520
thereby diminishing the efficacy of treatment” (Spec. 137). “Localized cell
delivery directly to a target site limits exposure of the administered cells to
the areas surrounding the target site. Localized cell delivery and cell
retention enables the administration of a controlled therapeutic dose” (Spec.
138).
“A biocompatible pre-formulation to form a biocompatible hydrogel
polymer matrix enables the administration and retention of cells directly to
target sites” and “provides structural and nutritional support for the cells
after administration of the polymer matrix or pre-formulation to a target site”
(Spec. 139).
The Claims
Claims 1—5, 7—14, and 16—19 are on appeal. Claim 1 is representative
and reads as follows:
1. A fully synthetic, polyglycol-based biocompatible hydrogel
polymer matrix comprising a fully synthetic, polyglycol-based
biocompatible hydrogel polymer comprising at least one first
monomeric unit bound through at least one amide linkage to at least
one second monomeric unit, wherein the polymer forms the matrix
that encapsulates:
(a) at least one cell; and
(b) a culture medium which supports the growth of the at least
one cell;
wherein the first monomeric unit is derived from a
MULTIARM-(5-50k)-NH2 or a MULTIARM-(5-50k)-AA monomer;
wherein the second monomeric unit is derived from a
MULTIARM-(5-50k)-SG, a MULTIARM-(5-50k)-SGA, or a
MULTIARM-(5-50k)-SS monomer; and
wherein the fully synthetic, polyglycol-based biocompatible
hydrogel polymer matrix provides controlled release of the at least
one cell, when implanted at a target site in an animal’s body, to the
target site of the animal’s body.
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The issues
A. The Examiner rejected claims 1—5, 7—14, and 16—19 under 35 U.S.C.
§ 103(a) as obvious over Askari2 and Boland3 (Ans. 2—5).
B. The Examiner provisionally rejected claims 1—5, 7—14, and 16—19 on
the ground of nonstatutory obviousness-type double patenting over the
claims of US 13/696,032 or 13/696,028, either in view of Boland (Ans. 6—
7).
A. 35 U.S.C. § 103(a) over Askari and Boland
The Examiner finds Askari teaches “a gelled mixture containing (i.e.,
a matrix that fully encapsulates) at least one or more therapeutic agents that
solidifies and releases the therapeutic agent(s) as the hydrogel degrades over
time (i.e., a controlled release) at the target/implantation site of a human’s
body” (Ans. 3). The Examiner finds that Askari teaches “the monomeric
units of the polymer are PEG-based” and “the first compound/monomeric
unit is or derived from an 8ARM-20k-NH2 and/or 8ARM-20k-AA and the
second compound/monomeric unit is or derived from a 4ARM-20k-SGA”
(Id.).
The Examiner acknowledges that Askari “differs from the present
claims by not specifying that the therapeutic agent is specifically at least one
mammalian stem cell in a culture medium that supports growth of the at
least one cell” (Ans. 4).
2 Askari et al., WO 2011/140517 A9, published Nov. 10, 2011 (“Askari”).
3 Boland et al., US 2008/0160085 Al, published July 3, 2008 (“Boland”).
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The Examiner finds Boland teaches “a hydrogel culture medium (para
[0012] and [0013]) that supports cell renewal and differentiation (i.e.,
growth) (para [0021]) and wherein the polymer may include, inter alia,
polyglycol-based polymers such as PEG and PLGA” (Ans. 4).
The Examiner finds it obvious
to modify the therapeutic agent in aqueous buffer of the
formulation of Askari et al by specifically substituting or
further comprising at least one mammalian stem cell in a
culture medium that supports growth of the at least one cell as
taught by Boland et al because Boland et al teach that
formulating biocompatible polyglycol-based matrix
formulations with mammalian stem cells in a culture medium
that supports growth of the at least one cell advantageously
allows for extensive therapy with numerous differentiated cells
that are enhanced at a target site for a therapeutically effective
period of time
(Ans. 5).
The issue with respect to these rejections is: Does the evidence of
record support the Examiner’s conclusion that Askari and Boland render
claim 1 obvious?
Findings of Fact
1. We limit our consideration of the merits of the appealed
rejections to the elected species. See Ex parte Ohsaka, 2 USPQ2d 1460,
1461 (Bd. Pat. App. Int. 1987). Thus, we limit our analysis to 8ARM-20k-
AA as the first monomer, 4ARM-20k-SGA as the second monomer, amide
as the specific linkage, and mammalian stem cell as the specific cell (see
Response to Restriction Requirement, filed June 20, 2014, 5).
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2. Askari teaches
An in vivo gelling pre-formulation to form a
biocompatible hydrogel polymer enables the administration of
medication directly to target sites. The polymer starts out as a
liquid pre-formulation and is delivered, with or without one or
more optional therapeutic agents, to the site of a disease using
minimally invasive techniques. . . . Once in the body, the liquid
pre-formulation polymerizes into a solid hydrogel that in some
instances adheres to the tissue and keeps the polymer/drug
combination at the site of the disease. In some instances,
polymerization and degradation times are controlled by varying
the composition of the monomers and buffers allowing for the
appropriate application and placement of the hydrogel polymer.
In some embodiments, the drug is released in a precise and
consistent manner.
(Askari 121).
3. Askari teaches:
In certain embodiments, mixing the first compound, the second
compound, and the optional therapeutic agent in the aqueous
buffer and delivering the mixture to a target site in the human
body generates the in vivo gelling pharmaceutical pre­
formulation such that the in vivo gelling pharmaceutical pre­
formulation at least in part polymerizes and gels at the target
site to form a biocompatible hydrogel polymer.
(Askari 125).
4. Askari teaches: “[sjuitable first compounds comprising a
nucleophilic group (used in the amine-ester chemistry) include, but are not
limited to . . . pentaerythritol polyethylene glycol amino acetate (4ARM-
PEG-AA) (molecular weight selected from about 5000 to about 40000, e.g.,
5000, 10000, or 20000). . . 4(or 8)ARM-PEG-AA” (Askari 130).
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5. Askari teaches: “[sjuitable second compounds comprising an
electrophilic group include, but are not limited to . . . pentaerythritol
polyethylene glycol succinimidyl glutaramide (4ARM-PEG-SGA)
(molecular weight selected from about 5000 to about 40000, e.g., 10000 or
20000)” (Askari 134).
6. Askari teaches: “In some embodiments, one or more first
compounds comprising an amino group react with one or more second
compounds comprising a succinimidyl ester group to form amide linked first
and second monomer units” (Askari 137).
7. Table 1 of Askari is reproduced below:
Table 1. Components used in formulations.
r--------------------------------------------------- 1------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ -
I Components j Technical Name
i 4ARM-20k-AA |4anrjPEG Acetate Amine HCL Salt. MW 20000 j
|8ARM-20k-NH2|8arm PEG Amine (hexa^yeeroi), HC1 Salt, MW 20000 I
| 8ARM-i5k-'SG jSarra PEG SuceimmidylGiutaratc (hexaglyceroi), MW 15000 j
ETTMP -1300 jBthoxyiated triimthylolpropane tri(3 -!tB)'caplopropionaic)
EX~ 190 jSorbitol polyglyc uiy! ether
4ARM-20k-SGA|4arm PEG Succir iinktyl Glutaramide (pentaerythritol), MW 20000
DDP jcispkfin; cisdianmiinedichluroplatinuftiOI)
DC.P jcarbopiafim cis-E iamtm»e( 1,1 >cycid>otajiedieari)oxy1ato)piatinum(l.l)
(Askari 1113).
8. Askari teaches, in Example 1, that:
The 4ARM-20k-AA and 8ARM-20k-NH2 (typically in
the range of 0.1 mmol arms equivalents) was intimately mixed
in a 50 mL centrifuge tube. A volume of phosphate buffer was
added to the tube via a micropipette such that the final percent
of solids in solution was 5 percent. The mixture was shaken
briefly before adding the appropriate amount of ester (8ARM-
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15k-SG). Immediately after adding the ester, the entire solution
was shaken for 5 to 10 seconds before letting it rest.
(Askari 1127).
9. Boland teaches “to harness stem cells from embryonic and
somatic sources to provide replacement cell therapies for genetic, malignant,
and degenerative conditions. Adipose derived endothelial cells are
pluripotent stem cells” (Boland 13).
10. Figure 1 of Boland is reproduced below:
Semi-porous Immaterial Localized cells
FIG. 1
“FIG. 1 depicts a cell delivery matrix. Arrows indicate localized endothelial
cells and the semi-porous biomaterial” (Boland 1 8).
11. Boland teaches “compositions and methods for improving the
efficacy of cell based therapies through use of a composition that
significantly mitigates migration of the cells from the site of delivery”
(Boland 12).
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12. Boland teaches the “cell delivery matrix used in the methods of
the invention may be comprised of any degradable, bioabsorbable or non-
degradable, biocompatible polymer. Exemplary three-dimensional culture
materials include polymers and hydrogels . . . Such injectable compositions
are prepared using conventional materials and methods know[n] in the art”
(Boland 1113-14).
13. Boland teaches: “Therapeutic agents that can also be localized
by the cell delivery matrix may include Transforming Growth Factor beta
(TGF[3 and TGF-[3-related proteins for regulating stem cell renewal and
differentiation” (Boland 121).
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.”
KSRInt’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007).
Wrigley found a “strong case of obviousness based on the prior art
references of record. [The claim] recites a combination of elements that
were all known in the prior art, and all that was required to obtain that
combination was to substitute one well-known . . . agent for another.” Wm.
Wrigley Jr. Co. v. Cadbury Adams USALLC, 683 F.3d 1356, 1364 (Fed.
Cir. 2012).
Analysis
We adopt the Examiner’s findings regarding the scope and content of
the prior art (Ans. 2—5; FF 1—13) and agree that the claimed device would
have been obvious over the teachings of Askari and Boland.
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Boland teaches a synthetic cell delivery matrix comprised of a
hydrogel that is degradable (FF 12), that encapsulates the cells (FF 10), and
that may include culture media growth factors such as TGF[3 (FF 13) for
delivery into a patient’s body (FF 11).
Askari teaches biocompatible hydrogel polymers with controlled
degradation for delivery to a patient’s body (FF 2) composed of polymer
mixtures (FF 3) where first polymers include 8ARM-PEG-AA in PEG sizes
of 5, 10, or 20K (FF 4), second polymers include 4ARM-PEG-SGA in PEG
sizes of 10 or 20K (FF 5), and amide linkages between the polymers (FF 6).
Askari exemplifies polymers comprising 4ARM-20k-AA and 8ARM-15k-
SG (FF 8).
We agree with the Examiner that “Boland et al teach that cells may be
used as therapeutic agents in polyglycol-based hydrogel matrix formulations
and it is prima facie obvious to substitute or combine one therapeutic agent
with another” (Final Act. 7).
We address Appellants’ arguments below.
Appellants contend “Boland cannot suggest the claimed specific
hydrogel polymer, because: 1) Boland only provides an innumerable and
practically infinite selection of matrix components, from which to select a
suitable polymer; and 2) Boland does not provide any hint of the specific
polyethylene glycol-based monomers that form the claimed hydrogel
polymer” (App. Br. 7). Appellants further contend that “Boland does not
teach the polymer elected in the response to the Restriction Requirement
mailed June 20, 2014, where the hydrogel polymer is made from 8ARM-
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20k-AA as the nucleophilic monomer and 4ARM-20kSGA as the
electrophilic monomer” (App. Br. 12).
We do not find this argument persuasive because the rejection is
based on obviousness over both Boland and Askari, not Boland alone.
Boland teaches that any degradable, biocompatible hydrogel polymer may
be used (FF 12) and Askari teaches a set of such polymers including the
specific polymer components elected by Appellants (FF 1—8). “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., Inc., 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.
We agree with the Examiner’s analysis that this combination falls
squarely within KSR’s guidance that the predictable combination of known
elements are likely obvious, and in particular, the selection of known
biocompatible hydrogel polymers used for agent delivery to patients from
Askari for use as the hydrogel polymers in Boland represents an obvious
known equivalent.
Appellants contend that “Boland offers a practically infinite number
of possible matrices from which to select, none of which are obvious to try
other than fibrin, collagen, expanded polytetrafluoroethylene, and
polyethyleneterephthalate, which are listed in Boland’s claims” (App. Br.
10).
We are not persuaded. It is well settled that it is a matter of
obviousness for one of ordinary skill in the art to select a particular
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component from among many disclosed by the prior art where it is taught
that the selection will result in the disclosed effect. See Merck & Co., Inc. v.
Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989) (“That the [prior art]
discloses a multitude of effective combinations does not render any
particular formulation less obvious.”); In re Corkill, 111 F.2d 1496, 1500
(Fed. Cir. 1985) (obviousness rejection affirmed in light of prior art teaching
that “hydrated zeolites will work” in detergent formulations, even though
“the inventors selected the zeolites of the claims from among ‘thousands’ of
compounds”). In the instant situation, Askari specifically identifies the
elected species as desirable components and exemplifies closely related
hydrogel polymers to those elected (FF 4—8).
Appellants contend that “Askari does not cure these deficiencies of
Boland, because Askari is focused on the delivery of compounds as
therapeutic agents . . . Askari does not mention anywhere the delivery of
viable cells” (App. Br. 12).
We remain unpersuaded by Appellants’ arguments regarding the
references separately. See In re Keller, 642 F.2d 413, 425 (CCPA 1981):
The test for obviousness is not whether the features of
a secondary reference may be bodily incorporated into
the structure of the primary reference; nor is it that the
claimed invention must be expressly suggested in any
one or all of the references. Rather, the test is what the
combined teachings of the references would have
suggested to those of ordinary skill in the art.
Appellants contend that:
Finally, there is no reason to expect that a formulation for
delivering chemical compounds, as provided in Askari, could
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be used to deliver a living cell, because a cell requires a specific
environment for viability and differentiation, which is not
required by a chemical compound. For example, a cell has a
complex outer membrane, which necessitates that a polymer
matrix encapsulating the cell does not lyse or significantly
disrupt the membrane so as to render the cell useless for its
provided function. Hence, a cell is not predicted to survive and
function in a matrix in the same manner as a chemical
compound.
Because the behavior of a living cell is unpredictable,
there is no reason to expect that any one of the polymer types
listed in Boland would function to encapsulate and deliver a
viable cell, especially as Boland does not provide any methods
or guidance for formulating a matrix from the long list of
generic polymers.
(App. Br. 13).
We find this argument unpersuasive. Boland is a published US patent
application and as such, “is presumptively enabling barring any showing to
the contrary by a patent applicant.” In re Antor Media Corp., 689 F.3d
1282, 1288 (Fed. Cir. 2012). Because Boland teaches stem cell delivery
using biocompatible hydrogels (FF 9-13) and Askari teaches that the
particular hydrogels are biocompatible (FF 2), the use of Askari’s
biocompatible hydrogels for delivery of Boland’s stem cells has a reasonable
expectation of success. “Obviousness does not require absolute
predictability of success ... all that is required is a reasonable expectation of
success.” In re Kubin, 561 F.3d 1351, 1360 (Fed. Cir. 2009) {citing In re
O’Farrell, 853 F.2d 894, 903-904 (Fed. Cir. 1988)).
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Appellants provide no evidence, other than Attorney argument,4 to
support the position that there is not a reasonable expectation of success or
that a cell would not survive in the biocompatible hydrogels disclosed by
either Boland or Askari, much less the specific embodiments preferred by
Askari (FF 7—8). “[Attorney argument [is] not the kind of factual evidence
that is required to rebut a prima facie case of obviousness.” In re Geisler,
116 F.3d 1465, 1470 (Fed. Cir. 1997).
Appellants contend the “only guidance for isolating certain
MULTIARM polyglycol-based monomers from Askari and combining them
with a cell comes from the Appellants’ claims and thus the rejection over the
combination of references is an exercise in impermissible hindsight” (Reply
Br. 6).
We are not persuaded. While we are fully aware that hindsight bias
may plague determinations of obviousness, Graham v. John Deere Co., 383
U.S. 1,36 (1966), we are also mindful that the Supreme Court has clearly
stated that the “combination of familiar elements according to known
methods is likely to be obvious when it does no more than yield predictable
results.” KSR, 550 U.S. at 416. In the instant case, selecting Askari’s
biocompatible hydrogel polymers used for therapeutic delivery into patients
for the biocompatible hydrogel polymers used to encapsulate stem cells for
deliver into patients as desired by Boland represent the selection of known
obvious equivalent polymers as expressly discussed by Boland (see FF 12;
4 We do not find Appellants’ footnote that “the toxicity of polymer
byproducts can be accurate and readily determined from sources that cannot
be reasonably questioned” as constituting evidence, only attorney argument
(see Reply Br. 5, footnote 1).
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“injectable compositions are prepared using conventional materials and
methods know[n] in the art”).
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that
Askari and Boland render claim 1 obvious.
B. Double Patenting
Appellants do not address this rejection in the Appeal Brief, and only
state in the Reply Brief that “[wjith regard to the provisional non-statutory
obviousness-type double patenting rejection over Appellants’ copending
applications US 13/696032 and US 13/696028 in view of Boland,
Appellants disagree for the reasons described in the non-obviousness
arguments” (Reply Br. 10).
To the extent that this represents an argument, even if untimely, we
find it unpersuasive for the reasons given above regarding the obviousness
rejection.
SUMMARY
In summary, we affirm the rejection of claim 1 under 35 U.S.C.
§ 103(a) as obvious over Askari and Boland. Claims 2—5, 7—14, and 16—19
fall with claim 1.
We affirm the provisional rejection of claims 1—5, 7—14, and 16—19 on
the ground of nonstatutory obviousness-type double patenting over the
claims of US 13/696,032 or 13/696,028, either in view of Boland.
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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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