Ex Parte Cantaluppi et al

Patent Trial and Appeal Board

Jun 30, 2016

12734160 (P.T.A.B. Jun. 30, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
121734, 160 04/15/2010
136 7590 07/05/2016
JACOBSON HOLMAN PLLC
400 Seventh Street N.W. Suite 700
Washington, DC 20004-2218
FIRST NAMED INVENTOR
Vincenzo Cantaluppi
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.
P73478USO 4642
EXAMINER
BEL YA VSKYI, MICHAIL A
ART UNIT PAPER NUMBER
1644
NOTIFICATION DATE DELIVERY MODE
07/05/2016 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):
patent@jhip.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte VINCENZO CANTALUPPI, MARIA CHIARA ARMILDE
DEREGIBUS, and GIOVANNI CAMUSSI1
Appeal2013-010633
Application 12/734, 160
Technology Center 1600
Before DEMETRA J. MILLS, KIMBERLY McGRAW, and TA WEN
CHANG, Administrative Patent Judges.
CHANG, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to methods
of treating type I or type II diabetes by pancreatic islet transplantation, which
have been rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We affirm.
STATEMENT OF THE CASE
The Specification states that, while pancreatic islet transplantation has
become "a rising therapeutic option" for the treatment of type I and type II
1 Appellants identify the Real Party in Interest as Fresenius Medical Care
Deutchland GmbH. (Appeal Br. 3.)
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Application 12/734, 160
diabetes," "a great percentage of transplanted islets still fails to engraft into
the liver after ... infusion .... " (Spec. 1.) The Specification states that
identification of factors capable of enhancing the functionality and survival
of transplanted islets is thus necessary to increase the success of the
procedure. (Id.) According to the Specification, the inventors have shown
that, when administered to a pancreatic islet transplant recipient,
microvesicles ("MV s") derived from endothelial progenitor cells ("EPCs")
are capable of promoting secretion of insulin from islet B-cells as well as
angiogenesis and formation of capillary-like structures from endothelial
cells. (Id. at 3.) Further according to the Specification, MV's adjuvant
effect "is not entirely inhibited by incubation with therapeutic doses of
rapamycin, the basic immunosuppressant [used] in pancreatic islet
transplantation." (Id.)
Claims 25-29 are on appeal. Claim 25 is illustrative and reads as
follows:
25. A method of treating type I or type II diabetes by pancreatic
islet transplantation, comprising administering microvesicles (MV s)
derived from a cell of the endothelial cell lineage to the transplant
recipient.
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The claims stand rejected as follows:
Claims 25-29 are rejected under 35 U.S.C. § 103(a) as being
unpatentable over the combination of Deregibus2 and Latta, 3 Peck, 4 or
Fournier. 5 (Ans. 3.)
DISCUSSION
Issues
The Examiner rejected claims 25-29 under 35 U.S.C. § 103(a) as
being unpatentable over the combination of Deregibus and Latta, Peck, or
Fournier. (Ans. 3.) The Examiner finds that Latta, Peck, and Fournier each
teaches "a method of treating type I and type II diabetes in human
comprising pancreatic islet transplantation" and further teaches "the use of
immunosuppression before and/or after transplantation." (Ans. 5.) The
Examiner finds that Latta, Peck, and Fournier do not explicitly teach
administering MV s derived from EPCs. However, the Examiner finds that
Deregibus teaches that "[EPC]-derived [MV s] can improve survival and
functionality of ... transplanted endothelial cells and promote angiogenesis
of said cells." (Id. at 6.) The Examiner concludes that the claims would
have been obvious because "[a ]ll the claimed elements were known in the
prior art[,] and one skill[ ed] in the art could have combine[ d] the elements as
claimed by known methods with no change in their respective function [to]
2 Maria Chiara Deregibus et al., Endothelial progenitor cell-derived
microvesicles activate an angiogenic program in endothelial cells by a
horizontal transfer of mRNA, 110 BLOOD 2440 (Oct. 1, 2007).
3 Latta, US 7,361,334 B2, issued Apr. 22, 2008.
4 Peck et al., US 6,703,017 Bl, issued Mar. 9, 2004.
5 Fournier et al., US 5,425,764, issued Jun. 20, 1995.
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Application 12/734, 160
yield predictable results." (Final Act. 5; see also Ans. 6.) The Examiner
also finds that "the fact that MV promot[ es] angiogenesis of transplanted
cells ... support[s] the ... obviousness rejection, since at the time the
invention ... the correlation between angiogenesis and diabetes" was well
known. (Ans. 6.)
Appellants admit that Peck, Fournier, and Latta disclose treating type
I and type II diabetes by pancreatic islet transplantation and that Deregibus
teaches that MV s derived from EPCs are able to trigger angiogenesis both in
vitro and in vivo. (Appeal Br. 11.) However, Appellants contend that the
obviousness rejection constitutes clear error because the claims recite a new
function, because there is no reason for a skilled artisan to combine the cited
prior art, and because Deregibus teaches away from the claimed invention.
(Id. at 12.) Appellants also contend that claims 27-28 are independently
patentable because they contain limitations relating to method and dosage of
administration not taught or suggested in the prior art, and that claim 29 is
further non-obvious because the subject matter of the claim evinces
unexpected results.
The issues with respect to this rejection are ( 1) whether the evidence
of record supports the Examiner's prima facie case of obviousness; (2)
whether Deregibus teaches away from the claimed invention; and (3)
whether Appellants have presented evidence of unexpected results that,
when weighed with the evidence supporting obviousness, shows claim 29
would not have been obvious.
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Findings of Fact
FF 1. Deregibus teaches that "EPCs may activate angiogenesis in
endothelial cells by releasing MV s able to trigger an angiogenic program."
(Deregibus, Abstract, 2444, 2447.)
FF2. Deregibus teaches that "MVs derived from EPCs are able to
trigger angiogenesis both in vitro and in vivo by a horizontal transfer of
mRNA to human micro vascular and macrovascular endothelial cells." (Id.
at 2446, 2447.)
FF3. Deregibus teaches that MV s derived from EPCs may also
"induce proliferation, apoptosis resistance, and in vitro organization in
capillary-like structures in HMECs [(human microvascular endothelial
cells)] and HUVECs [(human umbilical vein endothelial cells)]." (Id. at
2447; see also 2443.)
FF4. For in vivo studies of MY-induced angiogenesis, HMECs were
incubated with MVs before being implanted into mice. (Id. at 2442.)
FF5. Fournier teaches "an implantable bioartificial pancreas device"
having a chamber containing pancreatic islets and vascularizing chamber( s)
containing a matrix providing small capillary growth and preventing blood
clotting. (Fournier, Abstract.)
FF6. Fournier teaches that, in the case of transplanted cells such as
islets, lack of sufficient vascularization "will quickly result in injury and
death of the transplanted cells or[,] at best[,] ... a poor glucose-insulin
response .... " (Id. at 2:30-37.)
FF7. Fournier teaches that an object of its invention is to provide an
easily implantable bioartificial pancreas device that provides a site-specific
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natural, non-clotting blood supply to immunoprotected islets of Langerhans,
which will result in normalized blood glucose control for a patient with
diabetes. (Id. at 2:44--49.)
FF8. Peck relates to methods for growing functional islet-producing
stem cells ("IPSCs"), islet progenitor cells ("IPCs"), and !PC-derived islets
("Idls") in in vitro cultures. (Peck, Abstract.)
FF9. Peck discloses islet transplantation as a method for treating
diabetes. (See, e.g., id. at 3:60-65, 4:60-5:11, 10:52-54, 14:52-60, 17:41-
18:11.)
FFlO. Peck discloses that "[a]ngiogenesis-induced vascularization
results in direct arteriolar blood flow to mature islets" and that
"vascularization may act to increase further the number of B cells," which
are the insulin-producing cells in the pancreatic islet. (Id. at 3:49-53, 1 :56-
58.)
FF 11. Latta discloses a method of creating tolerance to transplanted
cells, tissue, or organs by first implanting a tolerizing dose of a cell or tissue
into a patient. (Latta, Abstract.)
FF12. Latta discloses transplanting pancreatic islet cells as a method
for treating diabetes. (Latta, 7:48-8:3, 12:30--42, 12:53-60, Examples 2, 3.)
Analysis
Claims 25 and 26
The evidence of record supports the Examiner's finding that the
claims are prima facie obvious. As for claims 25 and 26, Latta, Fournier,
and Peck each discloses treating diabetes by transplanting pancreatic islets.
(FF5, FF7, FF9, FF12.) Deregibus teaches that MVs derived from EPCs are
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able to trigger angiogenesis, or growth of new blood vessels, in transplanted
endothelial cells, as well as to induce proliferation and apoptosis resistance
of endothelial cells in vitro. (FF 1-FF 4.) It would have been obvious to a
skilled artisan to administer Deregibus' EPC-derived MV s during pancreatic
islet transplantation to ensure sufficient vascularization and to improve
survival of any transplanted islet endothelial cells, particularly in light of the
Examiner's finding that the correlation between angiogenesis and diabetes is
well-known at the time of the invention. (Ans. 6.) Appellants have not
provided persuasive evidence to rebut the Examiner's findings.
Appellants contend that there is no motivation to combine the
references. (Appeal Br. 13-14.) This argument is not persuasive for the
reasons discussed above. In particular, we disagree with Appellants'
position that no evidence in the record supports the Examiner's finding
regarding the known correlation between angiogenesis and diabetes at the
time of the invention (Reply Br. 4): Fournier discloses that sufficient
vascularization (i.e., formation of blood vessels) is necessary when
transplanting islet cells to prevent poor glucose-insulin response or
transplant injury or death (FF6); Peck likewise discloses that vascularization
may act to increase the number of insulin-producing islet B cells. (FF 10.)
Put another way, both the use of pancreatic islet transplant to treat
diabetes, and MV' s function in triggering angiogenesis and inducing
proliferation and apoptosis resistance in endothelial cells, are known in the
prior art. Thus, as the Examiner points out, "one skill[ ed] in the art could
have combine[ d] the elements as claimed by known methods with no change
in their respective function and the combination would have yield[ ed]
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predictable results .... " (Ans. 7.) Such a combination is obvious. KSR
Int'! Co. v. Teleflex Inc., 550 U.S. 398 (2007).
Likewise, we are not persuaded by Appellants' arguments that
Deregibus does not teach or suggest that MV s can act like an adjuvant factor
for transplanted cells (Reply Br. 3--4), that islet cells for transplant and MVs
are not taught by the prior art to be useful for the same purpose (id. at 6-7),
and that the Examiner improperly relied on the Specification as prior art (id.
at 7-8.) Regardless of whether the term "adjuvant factor" is mentioned in
Deregibus, Deregibus' disclosure of MVs' role in angiogenesis and
proliferation and apoptosis resistance in endothelial cells supports the
Examiner's prima facie case of obviousness as to the claims. Similarly, for
the reasons discussed above, a prima facie case of obviousness exists
independent of any reference to teachings from the Specification or
teachings that islet cells and MV s are useful for the same purpose.
Appellants also contend that the rejected claims are not obvious
because they disclosed a new use for MV s derived from EPCs. (Appeal Br.
12-13.) In particular, Appellants argue that Deregibus only suggests using
microvesicles to improve the survival and promote angiogenesis of
transplanted endothelial cells, whereas the claims recite using microvesicles
to treat diabetes. (Id.)
We are not persuaded. While a new use of a known composition may
be patentable, the method predicated on the alleged "new use" must
nevertheless be new and unobvious. In re Zierden, 411 F.2d 1325, 1329
(CCP A 1969). Here, treating diabetes with pancreatic islet transplantation is
not new. (FF5, FF7, FF9, FF12.) Likewise, as discussed above, given the
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known functions of EPC-derived MV s in angiogenesis as well as endothelial
cell proliferation and apoptosis resistance (FFl--4), and given the prior art
disclosures that sufficient vascularization is necessary for successful
pancreatic islet transplantation (FF6), we agree with the Examiner that
administering MV s when treating diabetes through islet transplantation
would have been obvious. We note that, as part of their "new use"
argument, Appellants appear to contend that MV s are administered in the
invention to promote insulin production from B cells (rather than for the
known purpose of angiogenesis). (Appeal Br. 12.) We are not convinced.
As an initial matter, this alleged use is not recited in the claims.
"Furthermore, Peck also discloses that vascularization may act to increase
the number of B cells. (FFlO.)
Finally, Appellants argue that Deregibus teaches away from the
claimed invention. (Appeal Br. 14-15.) More specifically, Appellants argue
that Deregibus represents an effort to effect regenerative therapy through use
of MV s in place of stem cell transplantation, whereas the rejected claims
require pancreatic islet transplantation. (Id.) According to Appellants, a
skilled artisan, on reading Deregibus, would be lead in a "no stem-cell
transplantation" direction divergent from the "pancreatic islet
transplantation" path taken by the Appellants. (Id. at 15.) We are not
persuaded. To the extent Deregibus suggests that MVs may take the place
of stem cells in regenerative therapy, it does not teach away from all
transplants, much less teach away from treating diabetes through pancreatic
islet transplantation. Pancreatic islets are not stem cells. Indeed, Deregibus
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explicitly teaches administering MV s with transplanted endothelial cells.
(FF2-FF4.)
Claims 27 and 28
Claim 27 depends from claim 26 and further requires that MV s be
administered by intravenous infusion. Claim 28 depends from claim 27 and
further requires MVs to be administered at a dose of between 0.1 and 10
micrograms/Kg recipient weight.
Appellants contend that these claims are not obvious for the additional
reason that they contain limitations regarding method of administration and
dosage amounts not suggested in the cited references. (Appeal Br. at 17.)
We disagree because we find this case analogous to the routine optimization
of a range or other variable within a claim. As our reviewing court has
explained, "discovery of an optimum value of a variable in a known process
is usually obvious." Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1368 (Fed.
Cir. 2007). We note, but find unpersuasive, Appellants' argument that the
method and dosage of administration were not recognized as result effective
variables. (Appeal Br. 17-18.) Deregibus, for instance, disclosed that MV
dosage amounts affected the angiogenic response. (Deregibus 2444.)
Claim 29
Claim 29 depends from claim 25 and additionally requires a step in
which transplant recipient is "subjected to rapamycin-based
immunosuppression before and/or during and/or after transplantation."
Appellants have not disputed that administering rapamycin-based
immunosuppression as part of pancreatic islet transplantation is known in
the art. Appellants contend, however, that the claim is not obvious because
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the subject matter of the claim evinces unexpected results. (Appeal Br. at
19.) In particular, Appellants argue that combining rapamycin-based
immunosuppression with EPC-derived MV administration is unexpected
because rapamycin is known to damage whole EPCs. (Id.) We do not find
this argument persuasive, at least because Appellants have cited to no
evidence why a skilled artisan would expect rapamycin to affect EPC-
derived MV s in the same manner as whole EPCs.
SUMMARY
We affirm the rejection of claims 25-29 as obvious over the
combination of Deregibus and Latta, Peck, or Fournier.
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. § l.136(a).
AFFIRMED
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