Ex Parte Gerstenblith et al

Patent Trial and Appeal Board

Aug 21, 2018

13251910 (P.T.A.B. Aug. 21, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
13/251,910 10/03/2011
54110 7590 08/22/2018
JOHNS HOPKINS TECHNOLOGY VENTURES
1812 ASHLAND AVENUE
SUITE 110
BALTIMORE, MD 21205
Gary Gerstenblith
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.
Pll231-02 1048
EXAMINER
BOSQUES, EDELMIRA
ART UNIT PAPER NUMBER
3763
MAIL DATE DELIVERY MODE
08/22/2018 PAPER
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.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte GARY GERSTENBLITH, JASON BENKOSKI,
JEFFREY BRINKER, GEORGE COLES,
CHAO-WEI HWANG, PETER JOHNSTON,
GORDON TOMASELLI, ROBERT G. WEISS, and
STEVEN P. SCHULMAN1
Appeal2017-008067
Application 13/251,910
Technology Center 3700
Before CHARLES N. GREENHUT, NATHAN A. ENGELS, and
ERIC C. JESCHKE, Administrative Patent Judges.
GREENHUT, Administrative Patent Judge.
DECISION ON APPEAL
STATEMENT OF THE CASE
Appellants appeal under 35 U.S.C. § 134(a) from a rejection of claims
1-3, 5, 9, 13, 22, 28-32, and 36-48. We have jurisdiction under 35 U.S.C.
§ 6(b).
We affirm.
1 Appellants identify the real party in interest as Johns Hopkins University.
App. Br. 4.
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Application 13/251,910
CLAIMED SUBJECT MATTER
The claims are directed to an intravascular, implantable bioreactor2
for delivery of paracrine factors. 3 Claim 1, reproduced below with emphasis
added, is illustrative of the claimed subject matter:
1. An intravascular implantable bioreactor, comprising:
a pouch; and
cells enclosed within the pouch, said cells being capable
of producing paracrine factors,
wherein the pouch is collapsible and expandable to be
intravascularly implantable,
wherein the pouch is semipermeable such that it provides
containment of the cells preventing the egress of the cells while
further providing a barrier that shields the cells from
immunological attack, and
wherein the pouch is capable of releasing out of the
pouch paracrine factors having a molecular weight greater
than 500,000 Daltons that enhance recovery of injured
myocardium.
REFERENCES
The prior art relied upon by the Examiner in rejecting the claims on
appeal is:
Dionne
Russell
Mizuno
Rojo
Berry
Amodei
us 5,916,554
US 2002/0081726 Al
US 2006/0034808 Al
US 2006/0136049 Al
US 2007/0042015 Al
US 2011/0028945 Al
June 29, 1999
June 27, 2002
Feb. 16,2006
June 22, 2006
Feb.22,2007
Feb. 3, 2011
2 "[B]ioreactor" is defined as "a collection of cells, in a housing, capable of
producing and releasing paracrine factors." Spec. ,r 14.
3 "[P]aracrine factors" are defined as "diffusible components produced by
one cell to affect another cell," and "diffusible components" are defined as
"any protein, growth factor, biomolecule, nutrient or fluid produced by the
cells housed in the bioreactor." Spec. ,r 14.
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Application 13/251,910
REJECTIONS
Claims 1-3, 5, 9, 13, 22, 28, 31, 32, 36, 37, 40, 41, 43, and 46 are
rejected under 35 U.S.C. § 103(a) as being unpatentable over Rojo in view
of Dionne and Mizuno.
Claims 29, 38, and 44 are rejected under 35 U.S.C. § 103(a) as being
unpatentable over Rojo in view of Mizuno, Dionne, and Russell.
Claims 30, 39, and 45 are rejected under 35 U.S.C. § 103(a) as being
unpatentable over Rojo in view of Mizuno, Dionne, and Berry.
Claim 42 is rejected under 35 U.S.C. § 103(a) as being unpatentable
over Rojo in view of Mizuno, Dionne, Russell, and Berry.
Claims 47 and 48 are rejected under 35 U.S.C. § 103(a) as being
unpatentable over Rojo in view of Mizuno, Dionne, and Amodei.
ANALYSIS
As an initial matter, we note that although the Examiner relies upon
several references in rejecting Appellants' claims, the present appeal centers
around only two of those references-Rojo and Mizuno--which can be
summarized as follows:
Rojo is directed to an implantable, intravascular system comprising a
pouch that contains cells, wherein the cells produce and release therapeutic
agents to the host. Rojo, Abstract. The pouch thereof "can be composed of
a porous polymer, alginate, or other materials known to one of skill in the art
... [which] optionally creates an immuno-barrier thereby shielding the cells
from the host's immune system, while allowing for exchange of nutrients to
the cells from surrounding body fluids." Rojo ,r 25. However, Rojo is
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Application 13/251,910
largely silent as to the specifics of the therapeutic agent(s) that could be
released by the cells in the pouch.
Mizuno is directed to the in vitro generation of a tissue culture within
a semi-permeable membrane, wherein the membrane has a molecular weight
cut-off (hereinafter, "MWCO") of greater than 100,000 Daltons. Mizuno,
Abstract. The semi-permeable membrane is selected "so as to retain cells,
any high molecular weight extracellular matrix elaborated by the cells, and
high molecular weight degradation products of the biodegradable hydro gel
carrier within the cell culture space." Id. ,r 11. In other words, the MWCO
of the membrane in Mizuno is an expression of the size of product that will
be retained within the culture space. Id. ,r 104.
In rejecting independent claims 1 and 36, the Examiner cites Rojo as
disclosing an intravascular implantable bioreactor comprising a pouch (31,
33) containing stem cells (20) capable of producing paracrine factors. Final
Act. 2-3, 5---6. However, the Examiner concedes that the Rojo pouch (i) is
not expandable and collapsible and (ii) is not semi-permeable so as to be
capable of releasing paracrine factors having a molecular weight greater than
500,000 Daltons. Id. at 3--4, 6-7. To cure these deficiencies, the Examiner
relies on Dionne as teaching an expandable and collapsible pouch. Id. at 4,
6-7. The Examiner also relies on Mizuno for teaching a semi-permeable
pouch capable of releasing paracrine factors greater than 500,000 Daltons.
Id. at 3, 6.
Appellants challenge the rejection for its reliance on Mizuno,
contending that the proposed Rojo-Mizuno combination would not have
been obvious to one of ordinary skill in the art for several reasons. We
address each in tum.
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First, Appellants argue the Examiner's rejection relies on
impermissible hindsight to arrive at the claimed invention. App. Br. 10.
Specifically, Appellants argue it would not have been obvious to combine
Rojo and Mizuno because "the desired function and results [of Rojo and
Mizuno] ... are opposite." Id. at 16. That is, Rojo's pouch performs a
therapeutic function by allowing desirable elements out of the device,
whereas Mizuno's semi-permeable membrane is selected for, and the
therapeutic product is obtained by, retaining desirable elements within the
device. Id. Consequently, according to Appellants, the proposed
combination would "render the Rojo invention entirely inoperable and
unsuitable for Rojo's and Appellants' claimed purpose." Id. at 13.
The Examiner states that Mizuno was relied upon "only to show that
there are other pouch membranes with a molecular weight cut off ranging
from O. lkDa to lOOOkDA, and that such membranes are chosen depending
on the molecular weight of the solute that will be retained in the membranes
and the solute that will be released." Ans. 12. Consequently, the Examiner
concludes, it would have been obvious to construct Rojo's pouch with a
semi-permeable membrane as taught by Mizuno, with the pore size thereof
being selected "depending on the disorder to be treated." Id. For the
reasons below, we agree with the Examiner.
A conclusion of obviousness may be supported by a showing that the
claims are directed to a process, machine, manufacture, or composition of
matter already known in the prior art that is altered by the mere substitution
of one element for another known in the field, and such modification yields
a predictable result. KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398,416 (2007)
(citing United States v. Adams, 383 U.S. 39, 40 (1966)). The Court in KSR
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further stated that "if a technique has been used to improve one device, and a
person of ordinary skill in the art would recognize that it would improve
similar devices in the same way, using the technique is obvious unless its
actual application is beyond his or her skill." KSR, 550 U.S. at 417. When
considering the obviousness of a combination of known elements, the
operative question is, thus, "whether the improvement is more than the
predictable use of prior art elements according to their established
functions." Id.
Appellants admit that "Mizuno does teach semi-permeable
membranes having molecular weight cut off ranges in the same range as
Appellants' claims." App. Br. 13. Thus, there is no dispute that the MWCO
range recited in claims 1 and 36 is already known in the art. Consequently,
the question here is whether applying Mizuno' s teaching of a particular
range of MWCO for a semi-permeable membrane to Rojo's pouch would
require "more than the predictable use of prior art elements according to
their established functions." KSR, 550 U.S. at 417. We conclude it would
not.
Rojo's functionality relies on the use of a porous pouch, whereby the
therapeutic agents that are produced in the pouch are delivered to the host by
passing through the pouch into the system of the host. Rojo, Abstract.
Furthermore, Rojo's functionality also relies on a balance between allowing,
on the one hand, desirable things (i.e., the therapeutic agents) out of the
pouch, while at the same time preventing undesirable things (e.g., the host's
immune system) from entering the pouch. Id. ,r 25. One way of achieving
such a balance would be for the pouch to have a specific
porosity/permeability, such that the flow of products into and out of the
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pouch could be regulated according to the molecular weight of the products.
This is precisely what Mizuno suggests, through its use of a semi-permeable
membrane having a MWCO that "is selected to retain cells, ECM, and high
molecular weight components of the biodegradable amorphous carrier, while
permitting exchange of low molecular weight degradation products of the
carrier, nutrients, waste products, and gases with the culture medium."
Mizuno ,r 104. Accordingly, one of ordinary skill in the art would recognize
that Rojo could be improved by the selection of a particular MWCO
membrane for the very same reason that feature improves Mizuno: it
provides enhanced control over what does, and does not, make its way into
the host's system.
As to Appellants' allowing-versus-retaining argument, Appellants
would have us hold that if a skilled artisan seeking to improve Rojo's pouch
were apprised of Mizuno' s membrane and the various ranges of MWCOs in
which it is commercially available (Mizuno ,r 7 6), the artisan would see no
potential in the Mizuno membrane merely because Mizuno employed it to
retain, rather than disperse. We disagree. Although the MWCO of the
Mizuno membrane is "selected to retain" (id. ,r 104), Mizuno expressly
acknowledges that "[ s ]emi-permeable membrane ... selectively allow[]
influx and efflux," of molecules based on size. Id. ,r 61 ( emphasis added).
Thus, given that the Mizuno membrane is capable of simultaneously
allowing certain things out while retaining certain things in, the membrane
would logically lend itself to incorporation into Rojo's pouch. See Rojo ,r 25
( describing the pouch as "shielding the cells from the host's immune system,
while allowing for exchange of nutrients to the cells from surrounding body
fluids").
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Accordingly, Appellants do not apprise us of error in the Examiner's
rejection owing to the use of impermissible hindsight reasoning.
Next, Appellants argue modifying Rojo by adding Mizuno's semi-
permeable membrane would not have been obvious because such a
modification would necessarily include two additional aspects of Mizuno,
both of which would be detrimental as to Rojo. App. Br. 17. First, adding
Mizuno's biodegradable carrier to Rojo would limit the time period over
which Rojo's device would be therapeutically effective. Id. at 17-18.
Second, the application of hydrostatic fluid pressure on the cells by
Mizuno' s bioreactor "could have detrimental effects on the function of the
cells contained in Rojo's device." Id. at 18.
The Examiner finds that these additional aspects of Mizuno are of no
relevance to the rejection because the Examiner relied on Mizuno merely "to
show a specific MWCO on a semi-permeable membrane[,]" and finds that
modifying Rojo in view of Mizuno would not require "substitut[ing] the
semi-permeable pouch of Rojo with the pouch and carrier of Mizuno[.]"
Ans. 16. For the reasons below, we disagree with Appellants.
"The test for obviousness is not whether the features of a secondary
reference may be bodily incorporated into the structure of the primary
reference." In re Keller, 642 F.2d 413,425 (CCPA 1981); see also In re
Nievelt, 482 F.2d 965, 968 (CCPA 1973) ("Combining the teachings of
references does not involve an ability to combine their specific structures.").
The Examiner's reliance on Mizuno is limited to the teaching of the
semi-permeable membrane. Final Act. 3. Consequently, Appellants'
argument rests on the assumption that when incorporating Mizuno' s
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membrane into Rojo, the membrane would necessarily bring with it
Mizuno's biodegradable carrier and hydrostatic fluid pressure. However,
Appellants do not apprise us of why the two additional aspects of Mizuno
are so interrelated to the semi-permeable membrane that incorporating the
latter into Rojo would require incorporating the former as well. Thus, even
if what Appellants allege about their incorporation into Rojo were true, it
would have no bearing on the Examiner's conclusion of obviousness.
Accordingly, Appellants do not apprise us of error in the Examiner's
rejection.
Finally, Appellants argue the Examiner has failed to give substantive
weight to Appellants' objective indicia of nonobviousness, which Appellants
contend collectively4 provides evidence of "the long-felt, and unmet need
for a method for regenerating cardiac tissue after heart damage, the failures
of prior art techniques for regeneration of cardiac tissue with stem cell
therapy, and the absence of any FDA approved treatment device and/or
regimen based on the prior art." App. Br. 21-22. The Examiner finds
Appellants' evidence is insufficient to overcome the Examiner's conclusion
of obviousness because it is not commensurate in scope with the claims.
Ans. 17. We agree with the Examiner that the evidence of obviousness
outweighs Appellants' evidence against.
In In re Piasecki, the Federal Circuit laid out the process by which an
Examiner is to consider rebuttal evidence:
4 Appellants' evidence of nonobviousness comprises the Declaration of Dr.
Gary Gerstenblith (hereinafter "the Gerstenblith Declaration"), submitted on
May 5, 2015, which incorporates by reference eight additional references
(hereinafter "the additional references"). App. Br. 38.
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When prima facie obviousness is established and evidence is
submitted in rebuttal, the decision-maker must start over. ...
An earlier decision should not, as it was here, be considered as
set in concrete, and applicant's rebuttal evidence then be
evaluated only on its knockdown ability. Analytical fixation on
an earlier decision can tend to provide that decision with an
undeservedly broadened umbrella effect. Prima facie
obviousness is a legal conclusion, not a fact. Facts established
by rebuttal evidence must be evaluated along with the facts on
which the earlier conclusion was reached, not against the
conclusion itself. . . . [A] final finding of obviousness may of
course be reached, but such finding will rest upon evaluation of
all facts in evidence, uninfluenced by any earlier conclusion
reached by an earlier board upon a different record.
In re Piasecki, 745 F.2d 1468, 1472-73 (Fed. Cir. 1984). Where, as here,
Appellants present evidence to establish long-felt need and the failure of
others, the relevance of such evidence to the issue of obviousness depends
on three factors. First, the need must have been a persistent one that was
recognized by those of ordinary skill in the art. In re Gershon, 372 F.2d
535, 539 (CCPA 1967). Second, the long-felt need must not have been
satisfied by another before the invention by applicant. Newell Cos. v.
Kenney Mfg. Co., 864 F.2d 757, 768 (Fed. Cir. 1988). Third, the invention
as claimed must in fact satisfy the long-felt need. In re Cavanagh, 436 F.2d
491,496 (CCPA 1971). To be given substantial weight in the determination
of obviousness or nonobviousness, evidence of secondary considerations
must be relevant to the subject matter as claimed and, therefore, Appellants
must establish a nexus between the merits of the claimed invention and the
evidence of secondary considerations. Ashland Oil, Inc. v. Delta Resins &
Refractories, Inc., 776 F.2d 281, 305 n.42 (Fed. Cir. 1985).
In this case, Appellants identify the persistent, recognized need within
the art as: "the long-felt, and unmet need for a method for regenerating
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cardiac tissue after heart damage ... with stem cell therapy." App. Br. 21-
22. Even assuming that this need is, in fact, "long-felt"-thereby satisfying
the first factor-we find Appellants' secondary evidence to be of
questionable relevance with regards to the second and third factors.
As to the second factor, we find the evidence does not tend to show
that the asserted long-felt need had remained unsolved by others. That is,
the evidence actually seems to show that stem cell therapy has already been
used, with various levels of success, to generate cardiac tissue. For instance,
the Hong reference indicates results from recent trials of cardiac stem cells
for cardiac repair are "quite promising." Gerstenblith Deel. 6, ,r 8.
Appellants seem to argue that their evidence shows failure by others because
it shows others have failed to solve the problem by using a pouch. Id. ,r,r 6-
8. However, the question under the second factor is whether the need had
been satisfied at all by another, not whether Appellants have satisfied the
need in a novel manner.
As to the third factor, we find the evidence does not tend to show that
the invention as claimed satisfied the need described. Specifically, like the
Examiner, we find nothing in the Gerstenblith Declaration or the additional
references shows that the success of Appellants' device in using stem cells
to regenerate cardiac tissue owes to the "greater than 500,000 Daltons"
requirement of claims 1 and 36. Put another way, there is no "nexus
between the merits of the claimed invention and the proffered secondary
considerations." Ashland Oil, 776 F.2d at 305 n.42. For example, paragraph
8 of the Gerstenblith Declaration amounts to little more than an argument as
to why Dr. Gerstenblith----one of the named inventors of the present
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application5-believes the Examiner's reliance on US 4,911,717 to Gaskill,
III in a previous Office action was improper. Gerstenblith Deel. ,r,r 7-9.
Such "evidence" is lacking a nexus to the invention as claimed because it
discusses a rejection of a previous version of the claims.
For the reasons above, we affirm the Examiner's rejection of claims 1
and 36. Appellants do not provide separate arguments as to dependent
claims 2, 3, 5, 9, 13, 22, 28-32, and 37--48. App. Br. 26-31.
DECISION
The Examiner's rejection of claims 1-3, 5, 9, 13, 22, 28-32, and 36-
48 is AFFIRMED.
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 ). See 37 C.F.R.
§ 1.136(a)(l )(iv).
AFFIRMED
5
"[ A ]n affidavit by an applicant or co-applicant as to the advantages of his
invention is less persuasive than one made by a disinterested person." In re
McKenna, 203 F.2d 717,720 (CCPA 1953).
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