Ex Parte Ghoroghchian et al

Patent Trial and Appeal Board

Mar 29, 2018

13508271 (P.T.A.B. Mar. 29, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/508,271 12/20/2012
22208 7590 04/02/2018
The Marbury Law Group, PLLC
11800 SUNRISE VALLEY DRIVE
15THFLOOR
RESTON, VA 20191
FIRST NAMED INVENTOR
P. Peter Ghoroghchian
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.
1597-00lUS 1543
EXAMINER
PURDY, KYLE A
ART UNIT PAPER NUMBER
1611
NOTIFICATION DATE DELIVERY MODE
04/02/2018 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):
ptonotices@marburylaw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte P. PETER GHOROGHCHIAN, MARK W. DEWHIRST, and
GREGORYM. PALMER
Appeal2017-001943
Application 13/508,271 1
Technology Center 1600
Before FRANCISCO C. PRATS, RACHEL H. TOWNSEND, and
DEVON ZASTROW NEWMAN, Administrative Patent Judges.
NEWMAN, Administrative Patent Judge.
DECISION ON APPEAL
This appeal under 35 U.S.C. § 134 involves claims to a method of
increasing efficacy of radiation or chemotherapy applied to a tumor in a
subject. The Examiner entered final rejections for obviousness.
We have jurisdiction under 35 U.S.C. § 6(b ).
We AFFIRM.
1 Appellants identify the real party in interest as "Vindico Nanobio
Technology, Inc. and Duke University." App. Br. 3.
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Application 13/508,271
STATEMENT OF THE CASE
Background
The Specification discloses that more than 50% of patients having
solid tumor malignancies patients "undergo radiotherapy (XR T) as part of
their treatment plan." Spec. i-f 3.
The ability of XR T to eradicate malignant cells depends
critically upon the intratumoral content of 0 2, a potent
radiosensitizer involved in mediating DNA damage. The
intratumoral 02 level is one of the most important determinants
of response among tumors of the same type treated with a
single fraction of ionizing radiation therapy.
Id. (citations omitted).
The Specification (i-f 2) discloses "methods for synthesis and delivery
of high-affinity oxygen binding agents to tumors to increase intratumoral
partial pressures of oxygen, mitigate the natural selection of tumor cells that
demonstrate aggressive molecular behavior and metastatic potential, and
potentiate the effects of radiation and chemotherapies."
The Claims
Claims 1-7, 13, 15, and 23-30 are on appeal. App. Br. 3. Claim 1,
the only independent claim on appeal, is illustrative and reads as follows:
1. A method of increasing efficacy of radiation or
chemotherapy applied to a tumor in a subject, comprising:
delivering a high-oxygen affinity agent to the tumor by
administering to the subject an oxygen carrier that incorporates
the high-oxygen affinity agent, wherein:
the high-oxygen affinity agent comprises a myoglobin
composition; and
the oxygen is released by the high-oxygen affinity agent at
oxygen tensions less than 10 mmHg, wherein the released
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oxygen diffuses out of the oxygen carrier while the high-
oxygen affinity agent remains within the oxygen carrier.
App. Br. 17 (Claims Appendix).
The Issues
The following rejections are before us to review:
Claims 1-7, 13, 15, 23-28, and 30 are rejected under pre-AIA
35 U.S.C. § 103(a) as being unpatentable over Winslow, 2 Galluzzo, 3 and
Arifin. 4 Ans. 2.
Claim 29 is rejected under pre-AIA 35 U.S.C. § 103(a) as being
unpatentable over Winslow, Galluzzo, Arifin, and Awasthi. 5 Id. at 4.
Because Appellants have waived arguments based on Awasthi (see Appeal
Br. 16), the same issue is dispositive for both rejections.
I
The Examiner finds that Winslow teaches methods for delivering
oxygen using a "hemoglobin-based oxygen carrier" that may be "unmodified
hemoglobin or modified hemoglobin," "encapsulated in a vesicle, such as a
synthetic particle, micro-balloon or liposome." Ans. 2. The Examiner finds
that Winslow teaches "delivery of oxygen to hypoxic inner cores of a tumor
mass increases sensitivity to radiotherapy and chemotherapy" but that
2 US 2003/0162693 Al, published August 28, 2003 ("Winslow").
3 Maria Galluzzo et al., Prevention of hypoxia by myoglobin expression in
human tumor cells promotes differentiation and inhibits metastasis, 119:4
THE J. OF CLINICAL INVESTIGATION 865-75 (2009) ("Galluzzo").
4 Dian R. Arifin & Andre F. Palmer, Polymersome Encapsulated
Hemoglobin: A Novel Type of Oxygen Carrier, 6 BIOMACROMOLECULES
2172-81 (2005) ("Arifin").
5 US 2011/0059157 Al, published March 10, 2011 ("Awasthi").
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Application 13/508,271
because of the unique microvasculature of a tumor, "sensitization through
increasing oxygen levels requires oxygen be unloaded within the hypoxic
core." Id. The Examiner finds that Winslow teaches the "partial pressure[]
of oxygen" or P50, which is the measurement of the pressure at which
oxygen is released to the surrounding tissues, "should be low to prevent
early unloading of oxygen, increasing the oxygen levels, to insure optimal
sensitization of the tumor to subsequent radiation and chemotherapy
treatments." Id.
The Examiner finds that Winslow does not teach myoglobin as the
high-oxygen affinity agent, but finds that "Galluzzo teaches that myoglobin
prevents hypoxic response in vitro and delays tumor engraftment and
reduces tumor growth following xenotransplantation into mice." Id. The
Examiner further finds that Galluzzo teaches that when tumors were
engineered to express [human] myoglobin, they displayed "reduced or no
hypoxia, minimal HIP-la levels and a homogenously low vessel density."
Id. at 2-3. The Examiner finds that Galluzzo teaches "myoglobin-mediated
tumor oxygenation promoted differentiation of cancer cells and suppressed
both local and distal metastatic spreading which were due primarily to
reduced tumor hypoxia." Id. at 3.
The Examiner finds that the skilled artisan would have found it
obvious to "to modify Winslow such that the particles comprised myoglobin
so as to provide oxygen to the tissues affected by hypoxia with a reasonable
expectation for success." Id.
The Examiner finds that Winslow and Galluzzo do not teach a particle
that encapsulates the myoglobin as being a polymersome with a particle size
of less than 100 nanometers. Id. However, the Examiner finds that Arifin
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teaches "polymersome encapsulated hemoglobin" and that "[t]he
hemoglobin loaded polymersome[ s] were extruded through a filter having a
pore size of 100 nm." Id. The Examiner concludes that, in light of "prior art
and general skill in manipulating/understanding said art, any person skilled
in the art would readily envisage reducing the particle size to a diameter of
less than 100 with a reasonable expectation in that the particle would be
useful for increasing radiation or chemotherapy efficacy." Id. The
Examiner concludes the skilled artisan would have found it obvious to
modify the method of Winslow to make therapeutic particles comprising
myoglobin "contained within a polymersome particle having a size less than
100 nm, as taught by Arifin, with a reasonable expectation for success in
arriving at a method of increasing efficacy of radiation or chemotherapy
applied to a tumor." Id. at 3--4.
Appellants contend that the cited references do not teach the claimed
invention, and that even if a prima facie case existed, evidence provided in
the declaration of Appellants' expert, Dr. Ghoroghchian, 6 is sufficient to
rebut the prima facie case. App. Br., passim.
The issue with respect to this rejection is whether a preponderance of
the evidence supports the Examiner's conclusion that Winslow, Galluzzo,
and Arifin suggest the claimed method of increasing efficacy of radiation or
chemotherapy applied to a tumor in a subject. We select claim 1 as
representative of the claims subject to this ground of rejection. 37 C.F.R.
§ 41.37(c)(l)(iv).
6 Declaration Pursuant to 37 C.F.R. § 1.132 of P. Peter Ghoroghchian,
executed November 27, 2014 ("Ghoroghchian Deel."). The declarant is an
inventor on the application.
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As stated in Jn re Oetiker, 977F.2d1443, 1445 (Fed. Cir. 1992):
[T]he examiner bears the initial burden ... of presenting a
prima facie case of unpatentability ....
After evidence or argument is submitted by the applicant
in response, patentability is determined on the totality of the
record, by a preponderance of evidence with due consideration
to persuasiveness of argument.
Here, Appellants do not persuade us that a preponderance of the
evidence fails to support the Examiner's conclusion that the claimed method
of increasing efficacy of radiation or chemotherapy applied to a tumor in a
subject would have been obvious to an ordinary artisan.
Unless otherwise indicated herein, we adopt the Examiner's findings
of fact, reasoning on scope and content of the claims and prior art, and
conclusions set out in the Final Action and Answer. Final Act. 7 5-9; Ans.
2-5. Only those arguments made by Appellants in the Appeal Brief and
properly presented in the Reply Brief have been considered in this Decision.
Arguments not so presented in the Briefs are waived. See 37 C.F.R.
§ 41.37(c)(l)(iv) (2015); see also Ex parte Borden, 93 USPQ2d 1473, 1476
(BP AI 2010) (informative) ("Any bases for asserting error, whether factual
or legal, that are not raised in the principal brief are waived.").
We agree with the Examiner (see Final Act. 5-9; Ans. 2-5) that the
skilled artisan would have found it obvious to combine the teachings of
Winslow, Galluzzo, and Arifin to practice the claimed method of increasing
efficacy of radiation or chemotherapy applied to a tumor in a subject. 8 As
7 Examiner's Final Act, mailed November 19, 2015 ("Final Act.").
8 As noted by the Appellants, (App. Br. 11-12) claim 1 does not require a
particle size of less than 100 nm. However, claim 11 recites that
"the nanoparticle is less than 100 nanometers in diameter." Id. at 19 (Claims
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found by the Examiner, Winslow teaches compositions comprising a
modified or unmodified oxygenated hemoglobin and having a high affinity
for oxygen that can be added in free form or encapsulated in a carrier such as
a liposome. Winslow, Abstract, i-fi-174--75. The skilled artisan would have
further learned by reading Winslow that when oxygen is delivered to the
inner core of a cancerous mass, radiotherapy and chemotherapy are more
effective against the mass, and that using a high-affinity oxygen carrier with
a low P50 would assist delivery of oxygen to the mass by preventing "early
unloading." Id. i-f 108.
We further agree with the Examiner that the skilled artisan would
have had a reasonable expectation of success in substituting myoglobin for
hemoglobin in the method of Winslow, given that myoglobin is shown in
Galluzzo to have a similar capability of enhancing oxygen use by hypoxic
tissues. See, e.g., Galluzzo 867 ("t]hese results suggest that Mb attenuates
the hypoxic response of cancer cells by enhancing their oxygenation during
hypoxia and allowing them to 'hold their breath' for short periods of time."),
871-873 (Mb supplies oxygen during hypoxia).
Indeed, Appellants' Specification acknowledges that myoglobin has a
very low P50, as is taught by Winslow (i-f l 08) to be important for oxygen
transfer in vivo. See Spec. i1 80 ("the oxygen dissociation curve of
myoglobin is a rectangular hyperbola with a very low P50"). As a result, we
agree with the Examiner (Ans. 3--4) that, upon reading Winslow, the artisan
would have had reason to substitute myoglobin, based on its low P50, for
Appendix). Accordingly, we adopt the Examiner's findings with regard to
Arifin as they relate to claim 27 only.
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hemoglobin in the method of Winslow to allow myoglobin to deliver oxygen
to combat tumor hypoxia, which was shown by Galluzzo to be an effective
treatment for reducing tumor activity, such as angiogenesis and metastasis,
(Galluzo 868, 869). It is obvious to those skilled in the art to substitute one
known equivalent for another. See In re Omeprazole Pat. Litig., 483 F .3d
1364, 1374 (Fed. Cir. 2007) (This court finds "no error in [the] conclusion
that it would have been obvious to one skilled in the art to substitute one
ARC [alkaline reactive compound] for another.").
We further agree that the skilled artisan would have learned from
Arifin that polymersome oxygen carriers could be created by loading them
with myoglobin, and extruding them through a filter having a pore size of
100 nm (Arifin, Abstract, 2173-2176) and we see no error in the Examiner's
conclusion that the skilled artisan would have found doing so "useful for
increasing radiation or chemotherapy efficacy" (Ans. 3--4).
We conclude the combined teachings of the references as a whole
would have suggested the claimed invention to the ordinarily skilled artisan.
In re Keller, 642 F.2d 413, 425 (CCPA 1981) (The test for obviousness is
what the combined teachings of the references, as a whole would have
suggested to those of ordinary skill in the art); KSR Int 'l Co. v. Teleflex Inc.,
550 U.S. 398, 416 (2007).
We have considered Appellants' arguments but do not find them
persuasive.
Appellants argue that the skilled artisan "would not have modified the
hemoglobin-based oxygen carriers taught in Winslow to provide a 'high-
oxygen affinity agent [comprising] a myoglobin composition,"' as claimed
based on Galluzzo' s disclosure because the proposed modification "would
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render the invention in Winslow improper for its intended purpose and/or
change the principle of operation." App. Br. 6. According to Appellants,
the Examiner's supposition that myoglobin can be substituted for
hemoglobin is erroneous because "Winslow relies on the fact that
hemoglobin is the most commonly used blood substitute" and related
findings while "Galluzzo discloses genetically modifying tumors to express
myoglobin, which is not useful for the improvements in blood substitutes to
which Winslow is directed." Id. at 6-7, 11. Appellants argue the skilled
artisan would not have been motivated to apply Galluzzo' s teachings on
myoglobin expressed by genetically-modified tumors to the HBOC
improvements disclosed in Winslow. Id. at 7. Appellants further argue the
proposed modification "to provide oxygen carriers comprising myoglobin
would frustrate the purpose of Winslow in creating effective, commercially
viable hemoglobin-based oxygen carriers." App. Br. 7.
We are not persuaded. That Winslow developed hemoglobin-based
carriers does not show that myoglobin-based carriers would not be effective.
Indeed, Winslow describes its goal as developing "blood substitutes and
plasma expanders. A blood substitute is a blood product that is capable of
carrying and supplying oxygen to the tissues." Winslow i-f 8. Galluzzo
demonstrates that myoglobin would be expected to be an effective substitute
for the delivery of oxygen, as discussed above. Appellants have not pointed
us to nor do we find any teaching in Winslow that discourages or excludes
any non-hemoglobin oxygen carrier for use with its methods. And even if
the purpose of Winslow is different, "the mere existence of differences
between the prior art and an invention does not establish the invention's
nonobviousness." Dann v. Johnston, 425 U.S. 219, 230 (1976). Moreover,
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Appellants do not provide evidence or persuasive argument that the skilled
artisan would have believed at the time of the invention that myoglobin was
an unsuitable high-oxygen affinity agent for use in the method of Winslow.
Attorney arguments and conclusory statements that are unsupported by
factual evidence are entitled to little probative value. See In re Geisler, 116
F.3d 1465, 1470 (Fed. Cir. 1997).
Appellants instead argue that statements in the Ghoroghchian
Declaration and the Specification support their argument that "myoglobin
does not share the properties of hemoglobin that enable hemoglobin to
maintain physiologic oxygen levels in all tissues within the body, and the
use of myoglobin is incompatible with the blood substitutes disclosed by
Winslow." App. Br. 7-8 (citing Spec.; Ghoroghchian Deel. i-fi-f 14--23);
Reply Br. 5---6. According to Appellants, "the different biochemical
pathways, mechanisms of action, and capabilities for binding and releasing
oxygen that exist for hemoglobin and myoglobin sufficiently demonstrate
that the proposed combination of Winslow and Galluzzo is improper." App.
Br. 8. Appellants cite teachings of the Specification including Figure 3 of
the Specification as evidence that the oxygen dissociation curves for
hemoglobin and myoglobin differ. Figure 3 is reproduced below:
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Application 13/508,271
_g
-~ ~
3j
'§ S{?~
::.~'
tfi
~ .....
Figure 3 "is a graph illustrating the oxygen dissociation curves of
hemoglobin and myoglobin." Spec. i-f 29. Appellants also cite the following
disclosure of the Specification:
FIG. 3 illustrates the oxygen dissociation curves of hemoglobin
and myoglobin, a ubiquitous protein involved in regulating
oxygen levels in muscle tissues. FIG. 3 shows that the oxygen
dissociation curve of myoglobin is a rectangular hyperbola with
a very low P50 that lies to the left of the sigmoid-shaped
hemoglobin oxygen dissociation curve (i.e., myoglobin has a
much higher affinity for oxygen than hemoglobin). That is, in
contrast to the example agents (e.g., Agent A, Agent B)
discussed above with reference to FIG. 2, myoglobin has an
oxygen dissociation curve that is shifted to the left of the
hemoglobin oxygen dissociation curve.
App. Br. 7 (citing Spec. i-fi-177-78, 80). Appellants further argue that
the "tetrameric structure" of hemoglobin is responsible for its ability
"to effectively transport oxygen in circulation, as required by the
invention disclosed in Winslow" and note that this structure is not
present in myoglobin. App. Br. 8 (citing Ghoroghchian Deel. i-fi-1 15-
23), 14; Reply Br. 3--4.
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The Examiner responds:
myoglobin P50 is about 130 pascals (Pa) while the P50 for
hemoglobin is about 3500 Pa and so in terms of using an
oxygen carrier for treating the hypoxic inner core of a tumor,
myoglobin would be a better choice than that of hemoglobin
given Winslow's admission that the oxygen carrier should have
a very low P50.
Ans. 6.
We are not persuaded that the Examiner erred. With regard to the
teachings of the cited art, we agree with the Examiner that Winslow teaches
that a low P50 is required for oxygen delivery to the hypoxic tumor.
Winslow i-f 108. Galluzzo teaches that "Mb functions as an oxygen supplier
when environmental p02 is low." Galluzzo 867. The Specification
acknowledges that myoglobin has a very low P50 (Spec. i-f 80) and
Appellants have not pointed us to teachings in the art otherwise. Thus, the
prior art disclosures and Appellants' Specification statements align with
rather than contradict the reasoning that myoglobin would be an equally
effective - if not better - high-affinity oxygen carrier for delivering oxygen
to hypoxic tumors. In addition, Galluzzo teaches:
Mb is a cytoplasmic heme protein that plays a well-
characterized role in oxygen transport and free radical
scavenging in skeletal and cardiac muscle cells (14, 15). Its
oxygen-related functions are multiple and include at least 3
different activities. First, Mb acts as an oxygen reservoir,
binding 0 2 in aerobic conditions and releasing it under hypoxia
. . . . Third, Mb supplements simple 0 2 diffusion by working as
a carrier in an activity known as facilitated 02 diffusion ....
We reasoned that if cancer cells expressed a similar
multifunctional oxygen transporter, the tumor as a whole would
(a) capture more oxygen from blood vessels, (b) benefit from a
more homogeneous oxygenation, and ( c) be less subject to
cycles of hypoxia and reoxygenation.
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Galluzzo 865-866. These teachings reinforce that the skilled artisan would
have recognized the suitability of myoglobin as an oxygen carrier and would
have expressly chosen to use it given the characteristics of the method
disclosed in Winslow.
Appellants further argue that the skilled artisan would have
understood "the known properties of myoglobin provide evidence that
myoglobin is specifically more harniful in circulation in a patient compared
to other heme-binding proteins." App. Br. 9. Appellants cite, for example,
the following Specification teaching:
While delivering high-oxygen affinity agents (e.g., myoglobin,
other synthetic proteins having similar oxygen affinity as
myoglobin, etc.) to solid tumors may improve the efficacy of
radiation therapy, in order to achieve proper localization to the
tumor, a large amount of the high-oxygen affinity agents must
be injected into the blood stream. Injecting a large amount of
such proteins into the bloodstream is dangerous, as the injected
agent (e.g., myoglobin) may be nephrotoxic and/or cause
hypertensive urgency or emergency (via sequestration of the
vasodilator nitric oxide that normally controls blood vessel
tone).
Spec. i-f 83 (emphasis added). Appellants also cite the Ghoroghchian
Declaration (i-fi-1 14--28 (e.g., "myoglobin does not share the properties of
hemoglobin that enable hemoglobin to maintain physiologic oxygen levels
in all tissues within the body, and the use of myoglobin is incompatible with
the blood substitutes disclosed by Winslow" and "one knowledgeable in
biochemistry would not expect myoglobin to be successful or safe for use in
systemic oxygen transport or to be able to specifically deliver oxygen only
to tumor tissues")). App. Br. 7-9. Appellants argue that the Ghoroghchian
Declaration "provides solid evidence that one of ordinary skill in the art
would not combine the teachings of Winslow and Galluzzo for a number of
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reasons," including the unpredictability of potential blood substitutes,
unsuitability of myoglobin for use as a blood substitute, and the inability to
express myoglobin in tumor tissue. Id. at 14--15. Appellants argue that the
Examiner "fails to properly address the evidence set forth in the Declaration
under 3 7 C.F .R. § 1.13 2 by Dr. Paiman Peter Ghoroghchian" and that the
Examiner's failure to do so in favor of the Examiner's own personal opinion
is error. Reply Br. 3--4.
The Examiner responds:
It is not and has not been the Examiner's position that
myoglobin would maintain physiologic oxygen level in all
tissues. Rather, the myoglobin is included to oxygenate the
hypoxic tissues of a tumor due to its low P50. Second, the
Examiner understands that tumors arise in various tissues
throughout the body which is why the invention of Winslow is
critical. Winslow teaches that their invention is capable of
reaching and oxygenating the hypoxic regions of tumors via
systemic administration that are otherwise unreachable.
Whether the oxygen carrier of the Winslow's method is
hemoglobin or myoglobin or both, the result would be alike in
that oxygen would be provided to the hypoxic target tissue so as
to sensitize the area to chemotherapy and radiation.
Ans. 9. 9 The Examiner further responds that the several points raised by the
Ghoroghchian Declaration are unpersuasive as the claim does not recite
9 We note the Examiner, in response to Appellants' assertion that certain
differences between hemoglobin and myoglobin demonstrate the
combination of Winslow and Galluzzo is improper, stated that the rejection
"is not suggesting that the myoglobin carrier be provided in place of
hemoglobin (whether of blood or synthetic carrier)." Ans. 6, 9. However, in
context, we understand the Examiner to have been indicating that the
rejection was not based on replacing hemoglobin as a blood substitute "to
maintain physiologic [oxygen] levels" in all tissues. Id. at 9. Rather the
myoglobin, is substituted "for the express purpose of oxygenating the
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systemic injection of myoglobin alone, the prior art suggests myoglobin as a
carrier is predictable, and that if the claimed method were toxic, Appellants'
own invention would be inoperable. Id. at 9-11.
Appellants reply that the Examiner has not addressed "the problems
with myoglobin administration" such as the disclosure in the Specification
that myoglobin injected into the bloodstream can be dangerous and cause,
e.g., "hypertensive urgency or emergency (via sequestration of the
vasodilator nitric oxide that normally controls blood vessel tone)" and the
conclusions stated in the Ghoroghchian Declaration that "one
knowledgeable in biochemistry would not expect myoglobin to be successful
or safe for use in systemic oxygen transport or to be able to specifically
deliver oxygen only to tumor tissues". Reply Br. 4--5.
We are not persuaded. The claims do not require, as Appellants
argue, that the high-oxygen affinity agent "maintain physiologic oxygen
levels in all tissues within the body", or injection into the bloodstream, but
instead that "the oxygen is released by the high-oxygen affinity agent at
oxygen tensions less than 10 mmHg." The record before us shows that
myoglobin will release oxygen at tensions less than 10 mmHg, as discussed
above. Moreover, the claims recite the use of an "oxygen carrier that
incorporates the high-oxygen affinity agent." As found by the Examiner,
Winslow teaches that "hemoglobin can be added to the blood product
hypoxic region of tumor" (id.), which Winslow "teaches that their
composition may be used for ... See [O 108]" (id. at 8). See also id. at 10
("The myoglobin would be provided in an amount sufficient to provide
oxygen to the hypoxic areas of a tumor mass and not replace the entirety of a
subject['s] hemoglobin.").
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composition in free form, or it may be encapsulated in a vessicle, such as a
synthetic particle, microballoon or liposome." Winslow i-f 75. The dangers
cited by Appellants' declarant relating to myoglobin relate to injection of
unencapsulated myoglobin into the bloodstream, not to use of myoglobin
encapsulated in a carrier such as a synthetic particle, as posited by the
Examiner. In that regard we note that the polymersomes used by Arifin to
deliver its oxygen-carrying protein are described as having camouflaging
ability. Arifin 2180. With regard to the remaining statements by
Ghoroghchian, we agree with the Examiner that none pertain to
requirements of the claims but rather speak to issues outside of the claims,
such as the inability of myoglobin to be expressed in tumor tissue. Because
Winslow teaches use of a carrier, as is required by the claims, we find that
Appellants have not demonstrated that the skilled artisan would have
believed the use of myoglobin would be dangerous to the patient and
consequently been inclined not to use it.
Appellants next argue that "Galluzzo expressly teaches away from a
method of systemic oxygen delivery because of the vascular irregularities
that by definition characterize the hypoxic tumors." App. Br. 10.
Galluzzo' s statement at issue is "it is uncertain whether increasing p02
systemically will result in enhanced oxygenation of a tumor that presents
manifest delivery flaws, due to the above discussed vascular abnormalities."
Galluzzo 865.
Under the proper legal standard, a reference will teach
away when it suggests that the developments flowing from its
disclosures are unlikely to produce the objective of the
applicant's invention. A statement that a particular
combination is not a preferred embodiment does not teach away
absent clear discouragement of that combination.
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Syntex (US.A.) LLC v. Apotex, Inc., 407 F.3d 1371, 1380 (Fed. Cir. 2005)
(citations omitted). We agree with the Examiner that Galluzzo's uncertainty
does not discourage use of a method of systemic oxygen delivery,
particularly because neither of the methods discussed by Galluzzo,
hyperbaric oxygen and systemic erythropoietin treatment, use carriers to
shield the oxygen from the system until it is in the region of the tumor, as
disclosed by Winslow and as recited in the claims.
Appellants next argue that Winslow does not teach or suggest "'the
released oxygen diffuses out of the oxygen carrier while the high-oxygen
affinity agent remains within the oxygen carrier,' as is recited in claim 1."
App. Br. 11. The Examiner does not respond to this argument directly, but
we do not find reason within Winslow to believe that the hemoglobin based
oxygen carrier (see, e.g., i-f 53) would release its oxygen and also -
separately- unbind itself from a carrier vehicle like a polymersome into the
bloodstream. Appellants' Specification describes the process of the high-
affinity oxygen agent inside a carrier releasing its oxygen as follows:
high-affinity oxygen binding agents may be encapsulated in
carrier vehicles having characteristics that allow for their
accumulation around tumor regions and/or are capable of
targeting tumors experiencing low oxygen tension. The carrier
vehicle may also have characteristics such that oxygen will
diffuse from within the vehicle to regions of low oxygen
tension (as exist in the center of tumors) while the high-affinity
oxygen binding agents remain encapsulated. The high-oxygen
affinity agents may be delivered to tumors in a manner that
allows the delivered agent to release oxygen at the oxygen
tension required to increase the efficacy of radiation due to the
oxygen partial pressure gradient characteristics of the agent.
Spec. i-f 85. This description is essentially identical to that described in
Winslow. See Winslow i-fi-175, 108. Appellants have not pointed to any
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teaching in Winslow suggesting the high affinity oxygen agent would also
dissociate from the carrier and we see no reason to believe it would, simply
because Winslow does not explicitly state that this event does not happen.
Conclusion of Law
For the reasons discussed above, we affirm the rejection of claim 1
under 35 U.S.C. § 103(a) based on Winslow, Galluzzo, and Arifin. Claims
2-7, 13, 15, 23-28, and 30 have not been argued separately and, therefore,
fall with claim 1. 37 C.F.R. § 41.37(c)(l)(iv).
II
Claim 29 stands rejected under 35 U.S.C. § 103(a) based on Winslow,
Galluzzo, Arifin, and Awasthi. Appellants have waived arguments based on
Hickey. Appeal Br. 16. We, therefore, affirm the rejection of claim 29 for
the reasons set out in the Examiner's Answer and as discussed above. See
37 C.F.R. § 41.37(c)(l)(iv) (Appeal Brief must contain "[t]he arguments of
appellant with respect to each ground of rejection."); Hyatt v. Dudas, 551
F.3d 1307, 1314 (Fed. Cir. 2008) ("When the appellant fails to contest a
ground of rejection to the Board, ... the Board may treat any argument with
respect to that ground of rejection as waived.").
SUMMARY
We affirm the rejection of claims 1-7, 13, 15, 23-28, and 30 under
pre-AIA 35 U.S.C. § 103(a) as being unpatentable over Winslow, Galluzzo,
and Arifin.
We affirm the rejection of claim 29 under pre-AIA 35 U.S.C. § 103(a)
as being unpatentable over Winslow, Galluzzo, Arifin, and Awasthi.
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Appeal2017-001943
Application 13/508,271
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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