Ex Parte Pupo Escalona et al

Patent Trial and Appeal Board

Nov 23, 2016

12159159 (P.T.A.B. Nov. 23, 2016)

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.
12/159,159 10/21/2008 Elder Pupo Escalona 976-54 PCT/US/RCE 4325
23869 7590 11/23/2016
Hoffmann & Rarnn T T P EXAMINER
6900 Jericho Turnpike
Syosset, NY 11791
ROMEO, DAVID S
ART UNIT PAPER NUMBER
1647
MAIL DATE DELIVERY MODE
11/23/2016 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 ELDER PUPO ESCALONA,
ROLANDO PAEZ MEIRELES,
JORGE AMADOR BERLANGA ACOSTA, and
BLAS YAMIR BETANCOURT RODRIQUEZ1
Appeal 2014-000387
Application 12/159,159
Technology Center 1600
Before ULRIKE W. JENKS, ROBERT A. POLLOCK, and
TAWEN CHANG, Administrative Patent Judges.
CHANG, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
method for treating diabetic foot ulcers, which have been rejected as
obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
1 Appellants identify the Real Party in Interest as Centro de Ingenieria
Genetica y Biotecnologia. (Appeal Br. 1.)
Appeal 2014-000387
Application 12/159,159
STATEMENT OF THE CASE
According to the Specification, “Diabetes Mellitus and its
complications is the main non-traumatic cause of lower limb amputations.
. . . At least 15% of diabetic patients develop chronic ulcers in their feet
throughout their lifetimes[;] 20% of these patients are estimated to require
lower limb amputation.” (Spec. 1:11—21 (citations omitted).) Further
according to the Specification,
[t]he present invention is related to topical formulations that
contain epidermal growth factor (EGF) encapsulated in or
associated to deformable or conventional liposomes to be
applied on the surface of and around chronic ischemic skin
lesions, for preventing diabetic foot amputation.
(Id. at 1:5-8.)
Claims 1, 2, 3, and 10 are on appeal. Claim 1, the only independent
claim, is illustrative and reproduced below:
1. A method for treating diabetic foot ulcers having a
grade IV or V skin lesion for preventing diabetic foot
amputation, said method comprising topically administering an
effective amount of epidermal growth factor encapsulated in or
associated to liposomes thereby achieving a complete
epithelization of the lesion and preventing foot amputation.
(Appeal Br. 9 (Claims App’x).)
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The Examiner rejects claims 1—3 under 35 U.S.C. § 103(a) as being
unpatentable over Brown,2 Acosta,3 Kaneko,4 Lundquist,5 and Hinz.6 (Ans.
3.)
The Examiner rejects claims 1 and 10 under 35 U.S.C. § 103(a) as
being unpatentable over Brown, Acosta, Kaneko, Lundquist, Hinz, Cevc
’500,7 and Cevc Article.8 (Ans. 6.)
DISCUSSION
Issue
The Examiner has rejected claims 1—3 under 35 U.S.C. § 103(a) as
being unpatentable over Brown, Acosta, Kaneko, Lundquist, and Hinz. The
Examiner further rejects claims 1 and 10 under 35 U.S.C. § 103(a) as being
unpatentable over the combination of these references in conjunction with
Cevc ’500 and Cevc Article. Because the same issue is dispositive for both
rejections, we address them together.
The Examiner finds that Brown discloses that “EGF accelerated
epidermal regeneration of donor sites and chronic non[-]healing diabetic
ulcers,” that “prolonged continuous exposure of EGF [is important] to
stimulate wound healing,” and that “[significantly higher levels of EGF
2 Gregory L. Brown et al., Acceleration of Tensile Strength of Incisions
Treated with EGF and TGF-fi, 208 Annals of Surgery 788 (1988)
(“Brown”).
3 Acosta et al., US 2005/0107294 Al, published May 19, 2005 (“Acosta”).
4 Kaneko et al., US 6,635,674 Bl, issued Oct. 21, 2003 (“Kaneko”).
5 Lundquist, US 3,990,445, issued Nov. 9, 1976.
6 Hinz et al., US 2009/0011000 Al, published Jan. 8, 2009 (“Hinz”).
7 Cevc, US 6,165,500, issued Dec. 26, 2000 (“Cevc ’500”).
8 Gregor Cevc, Lipid vesicles and other colloids as drug carriers on the skin,
56 Advanced Drug Delivery Reviews 675 (2004) (“Cevc Article”).
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were retained in incisions for extended periods by multilamellar liposomes
entrapping EGF.” (Ans. 3 4.) The Examiner also finds that, as shown by
Hinz, “[i]t is also well-known in the art that incorporation of peptides into
liposomes increases resistance to degradation by proteases.” {Id. at 5.)
The Examiner finds that Brown “does not expressly teach treating
advanced diabetic foot ulcers, wherein said advanced diabetic foot ulcer is a
grade IV or V ischemic skin lesion.” {Id. at 4.) However, the Examiner
finds that Acosta teaches “a method of treating a diabetic foot ulcer
comprising perilesionally injecting said ulcer with EGF, wherein said ulcer
is grade IV or V . . .,” and where “[t]he wounds were fully or completely re-
epithelialized and amputations were prevented.” (Id. (citations omitted).)
Finally, the Examiner finds that “[t]he disadvantages of injection are
well known in the art.” {Id. at 5.) In particular, the Examiner finds that
Lundquist teaches that “injection creates a danger of infection” and Kaneko
teaches that “topical application and percutaneous absorption of drugs
avoids the pain accompanying injection.” {Id.)
The Examiner concludes that
it would have been obvious to one of ordinary skill in the art at
the time of Applicants’ invention to treat wounds by a method
comprising administering an effective amount of EGF
encapsulated in or associated to liposomes, as taught by Brown,
and to modify that teaching by treating an advanced diabetic
foot ulcer, wherein said ulcer is grade IV or V ischemic skin
lesion, as taught by . . . Acosta, with a reasonable expectation of
success. One of ordinary skill in the art would be motivated to
make this modification because: prolonged continuous
exposure of EGF is important for stimulation of wound healing;
EGF in multilamellar liposomes would provide prolonged, local
delivery of EGF to the wound; EGF is useful for treating
chronic non[-]healing diabetic ulcers or advanced diabetic foot
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ulcers, wherein said ulcers are grade IV or V ischemic skin
lesions; pain and risk of infection accompany injection; topical
application and percutaneous absorption of drugs avoids the
pain accompanying injection; and incorporation of peptides into
liposomes increases resistance to degradation by proteases.
(Id. at 5—6.)
As to claim 10, which depends from claim 1 and additionally requires
that the liposome be a deformable liposome, the Examiner finds that
Cevc ’500 teaches combining EGF with transfersomes, which are
deformable. (Id. at 7.) The Examiner further finds that both Cevc ’500 and
Cevc Article teach the benefits of transfersomes, such as “the capability of
transporting materials into and through a permeability barrier.” (Id. at 7—8.)
The Examiner finds that it would have been obvious to a skilled artisan to
modify the teachings of Brown, Acosta, Kaneko, Lundquist, and Hinz with
deformable liposomes, with a reasonable expectation of success, in order to
take advantage of the benefits of such liposomes as described in the Cevc
references. (Id. at 8.)
Appellants contend that,
at the time the invention was made, one [sjkilled in the art
would not have a reasonable expectation of success in treating
diabetic foot ulcers having a grade IV or V skin lesion for
preventing diabetic foot amputation by topically administering
EGF in or associated to liposomes thereby achieving a complete
epithelization of the lesion and preventing foot amputation, as
claimed.
(Appeal Br. 5—6.)
The issue with respect to this rejection is whether a skilled artisan at
the time of the invention would have had a reasonable expectation of success
in combining the cited prior art to arrive at the claimed invention.
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Findings of Fact
1. Brown teaches that “enhance[d] wound healing result[s] in
accelerated gain of tensile strength in incisions.” (Brown 792.)
2. Brown teaches that “[rjepeated topical application of EGF
accelerated epithelial regeneration of primate corneas and epidermal
regeneration in pigs and increased tensile strength of unsutured corneal
incisions.” {Id. at 788, right column.) Brown further teaches that “repeated
applications of EGF induced hyperplastic regeneration of tympanic
membrane perforation in cats (unpublished data).” {Id. at 793, left column.)
3. Brown teaches that “[rjepeated topical treatment of partial­
thickness bums with EGF accelerated epidermal regeneration when EGF
was formulated in vehicles that prolong the exposure of residual epithelial
cells to EGF.” {Id. at 793, left column.)
4. Brown teaches that “[sjignificantly higher levels of [EGF] were
retained in incisions for extended periods by multilamellar liposomes
entrapping EGF.” {Id. at 791, left column.)
5. Brown teaches that, although average tensile strength of
incisions treated with single dose EGF without liposomes was not
significantly different than control, “an early increase in tensile strength was
stimulated when a single dose of EGF was delivered in delayed release
formulation (multilamellar liposomes), such that there was prolonged
exposure of growth factor to the wound.” {Id. at 790, right column; 792,
right column.) Additionally, Brown teaches that “the vehicle used to deliver
EGF to incisions is a key component.” {Id. at 792, right column.)
6. Brown teaches that, “[i]n a recent clinical trial, biosynthetic
human EGF accelerated epidermal regeneration of. . . chronic nonhealing
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diabetic ulcers (unpublished data). ... An extract of platelets containing
growth factor activity stimulated healing in chronic skin ulcers.” (Id. at
793.)
7. Acosta “relates to the use of. . . EGF ... in a preferably-
injectable pharmaceutical composition which is administered by means of
infiltration into and around chronic cutaneous ischaemic lesions in order to
prevent diabetic foot amputation.” (Acosta Abstract.)
8. Acosta teaches that “severe ischemic ulcers referred as in stages
IV and V according to Wagner classification have been treated and healed”
using the composition of its invention. (Id. at 111; see also id. at
137 (describing wounds treated as corresponding to “diabetic limb chronic
ulcers” and further stating that “[sjtages IV or V according to Wagner’s
classification predominated for ah the wounds”).)
9. Acosta describes treating 9 patients via “deep perilesional
infiltrations” using the composition of its invention and reports that
“[i]n all the patients treated toes, foot, [and] major amputation[] procedures
were prevented.” (Id. at 142; see also id. at || 43—51 (Examples 1—9).)
10. Kaneko relates to “an anti-inflammatory and analgesic
pharmaceutical preparation for external use having excellent percutaneous
absorption and applicability,” comprising non-steroidal anti-inflammatory
and analgesic agents (NSAIDs) and a percutaneous absorption promoting
agent such as oleic acid, oleyl alcohol or a mixture thereof. (Kaneko
Abstract.)
11. Kaneko teaches that the “dermatologic, topical, NS AID
containing pharmaceutical preparation of [its] invention possesses excellent
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percutaneous absorptive properties and when used in therapy can . . . avoid
the pain accompanying NSAID injection.” {Id. at 3:9-15.)
12. Lundquist relates to “[a] drug injection device . . . comprising]
a doubled wall, doughnut-shaped cylinder adapted to be inserted into an
intravenous delivery tube.” (Lundquist Abstract.)
13. Lundquist teaches that
[i]t is a common practice in hospitals to introduce drugs to a
patient through an intravenous feeding line whenever that
patient is being fed intravenously. It is obvious that such a
practice avoids the pain of repeated injections which
accompany direct injection from a hypodermic needle, but it
also avoids the danger of infection.
{Id. at 1:5-11.)
14. Hinz’s teaches infection inhibitors and protein expression, and
relates to certain fusion inhibitor peptides that may be used as medicaments.
(Hinz Abstract, 12.)
15. Hinz teaches “a pharmaceutical composition comprising (a) a
peptide of [its] invention and (b) a pharmaceutical carrier.” {Id. at | 87.)
16. Hinz teaches that, “[i]n preferred embodiments, the carriers are
liposomes.” {Id. at 190.) Hinz teaches that a peptide, gp41ctm,
incorporated into liposomes was not cleaved by protease under conditions
that otherwise cleaved the peptide, indicating that the peptide incorporated
into liposomes had increased protease resistance. {Id. at 1194.) Hinz
teaches that “[t]he protease resistance of liposome-incorporated [gp41ctm]
makes it particularly well suited for topical administration.” {Id. at 1195.)
17. Cevc ’500 teaches that an object of its invention is “to introduce
a new class of carrier preparations for the transport of drugs through human
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. . . skin, which result in a characteristic improved availability of the agent
molecules at the target site.” (Cevc ’500 3:13—17.)
18. Cevc ’500 teaches that
[t]he main requirement of. . . [its] drug carrier [suitable for the
penetration into and through a permeability barrier]—... a
transfersome—is that it is sufficiently elastic to penetrate
through the constrictions in a barrier, such as skin. In the case
of transfersomes consisting of phosphatidylcholine and sodium
cholate this condition is fulfilled when the edge tension of a
carrier is below 10 Piconewton; similar values are also likely to
pertain to other, related systems. Carriers which are capable of
creating a gradient after an application are particularly useful;
this is due to the fact that they have a spontaneous tendency for
penetration through permeability barriers.
{Id. at 2:57—3:4; see also id. at 49:15—51:2 (discussing the basic criteria for
carriers mediating the transport of agents through permeation barriers).)
19. Cevc ’500 teaches that
transfersomes can mediate transport of agents through
essentially all permeability barriers and are suitable, for
example, for percutaneous (dermal) applications of medical
agents. Transfersomes can carry water- or fat- soluble agents to
various depths at the application site, depending on the
transfersomal composition, application dose, and form. Special
properties which cause a carrier to behave as a transfersome can
be realized for phospholipid vesicles as well as for other types
of amphiphile aggregates.
{Id. at 4:57-65.)
20. Cevc ’500 teaches that suitably formulated transfersomes allow
introduction of
a major proportion of the drugs applied . . . not only into a
permeability barrier, such as skin, but, moreover, . . . into the
deeper tissues where they become systemically active.
Transfersomes can carry polypeptides, for example, through
intact skin at an effectiveness which is a 1,000 times higher
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than was previously possible when using structureless
penetration enhancers. Transfersomally formulated substances
can reach nearly 100% of the corresponding biologically or
therapeutical maximum efficacy after applications on human
skin. Similar effects, to date, have only been achievable by
using an injection needle.
{Id. at 4:66—5:11.)
21. Cevc ’500 teaches that “[tjransfersomes ... are suitable for the
application of many different agents ... for therapeutic purposes,” and
further teaches that the preparations according to its invention can contain an
agent for the treatment of wounds, such as growth stimulating factors, as
well as a “substance which affects growth in humans or animals, such as . . .
epidermal growth factor (EGF).” {Id. at 19:66—20:2, 31:20-26, 31:53—61.)
Cevc ’500 further discloses that (Cys(Acm(20, 31)-epidermal growth factor
and its fragments or receptors are “worth mentioning,” among others, as
“[pjeptides with a particularly high biological and/or therapeutic
significance, and which can also be combined with transfersomes.” (Id. at
39:48-50, 40:53-^1:11-12.)
22. Cevc Article teaches that the ability of colloids to cross the skin
barrier is “governed by colloid adaptability, which must be high enough to
allow penetrant deformation to the size of a pore in such barrier.” (Cevc
Article Abstract.)
23. Cevc Article teaches that
[tjransdermal drug delivery systems based on . . . drug
formulations [corresponding to compact colloids] rely on
simple drug diffusion through the skin .... In contrast, the
adaptability-[]and stability-optimised mixed lipid vesicles
(Transfersomes®, a trademark of IDEA AG) can trespass much
narrower pathways between most cells in the skin ....
Sufficiently stable ultra-adaptable carriers, therefore, can ensure
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targeted drug delivery deep below the application site. . . .
Drug delivery by means of highly adaptable drug carriers,
moreover, allows highly efficient and well-tolerated drug
targeting into the skin proper. Sustained drug release through
the skin into systemic blood circulation is another field of
ultradeformable drug carrier application.
(Id.; see also id. at 701—702 (bridging paragraph), 703.)
24. In particular, Cevc Article teaches that “[conventional
liposomes do not cross the skin efficiently, but can modulate drug
permeation into/through the barrier from the superficial lipid reservoir.” (Id.
at 698, left column.)
25. In contrast, Cevc Article teaches that “[ljipid bilayer
fluidity/vesicle deformability is a prerequisite for barrier penetration.” (Id.
at 698, left column; see also id. at 695, left column (stating that “barrier
penetrability to a colloid suspension increases with vesicle deformability and
volume exchange capability,” which in turn “depend on the average
membrane composition and on the reversible bilayer ingredients demixing
during transport”) (citations omitted), 701 (discussing examples where drug-
loaded Transfersomes® applied on skin resulted in carrier-mediated drug
transfer across the skin or biological activity).)
26. Cohen9 discloses that authors of prior art study (Brown et al.)
involving application of EGF in silver sulfadiazine cream to “patients with
variations in severity of thermal injury and age” concluded that “human
epidermal growth factor enhanced donor-site healing.” (Cohen Abstract,
251, left column.) Cohen further discloses that “[ajnimal studies have
91. Kelman Cohen et al., Topical Application of Epidermal Growth Factor
onto Partial-Thickness Wounds in Human Volunteers Does Not Enhance
Reepithelialization, 96 Plast. Reconstr. Surg. 251 (1995) (“Cohen”).
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indicated that epithelialization of wounds is enhanced by epidermal growth
factor.” (Id. at 251, right col.)
27. Cohen discloses that its study is “designed to determine the
effectiveness of human epidermal growth factor in accelerating the rate of
healing of partial-thickness human skin wounds of the same thickness in
healthy volunteers” by comparing effect on wound of human EGF-silver
sulfadiazine cream and silver sulfadiazine alone. (Id.)
28. Cohen found no statistically significant difference between
wound healing in sites receiving EFG and those receiving silver sulfadiazine
alone. (Id. at 252—253.) Cohen concludes that,
[although epidermal growth factor has been associated with
accelerated healing in several animal models, one hypothesis
suggests that epidermal growth factor requires the presence of
one or more other growth factors in order to accelerate the rate
of healing. ... In addition, the wound site may contain
proteolytic enzymes that would destroy the topically applied
growth factor. . . .
The differences in the Brown et al. report may relate to
differences in donor-site thickness .... Also, Brown et al. used
patients who may have had some depletion or inhibition of
epidermal growth factor secondary to infection or
immunosuppression as opposed to healthy volunteers.
The procedure outlined for this evaluation affords a unique
opportunity to evaluate partial-thickness wounds in healthy
volunteers without the complications of disease processes.
(Id. at 253, right column.)
Analysis
We adopt the Examiner’s findings of fact and reasoning regarding the
scope and content of the prior art. (Ans. 3—15; FF1—28.) We note in
particular that Brown teaches that repeated topical application of EGF
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accelerated epithelial and epidermal regeneration and enhanced wound
healing, particularly where EGF is formulated in vehicles that prolong the
exposure of residual epithelial cells to EGF (FF1—FF3); that Brown also
teaches that in a clinical trial EGF accelerated epidermal regeneration of
chronic nonhealing diabetic ulcers (FF6); and that Acosta teaches use of
EGF in a preferably injectable pharmaceutical composition to treat stage IV
and V diabetic ulcers and prevent diabetic foot amputation (FF7—9). While
Brown does not teach treating stage IV and V diabetic ulcers and preventing
diabetic foot amputation and Acosta does not teach topical application of
liposomes-associated EGF, we note that “the expectation of success need
only be reasonable, not absolute.” Pfizer, Inc. v. Apotex, Inc., 480 F.3d
1348, 1364 (Fed. Cir. 2007). Accordingly, we agree with the Examiner that
the combination of cited references provides a skilled artisan with a
reasonable expectation of success with respect to the claimed method.
With respect to the Examiner’s rejection of claims 1 and 10 over
Brown, Acosta, Kaneko, Lundquist, Hinz, Cevc ’500, and Cevc Article, we
further note that the Cevc references together teach deformable drug carriers
that, when topically applied with a drug, are capable of achieving therapeutic
effects similar to those achievable by using an injection needle. (FF17—25.)
This teaching further supports the Examiner’s finding that a skilled artisan
would have a reasonable expectation of success in arriving at the claimed
invention in light of the prior art.
Appellants rely on the Meireles Declaration10 and Cohen in support of
their argument that “the cited references neither individually nor collectively
10 Declaration of Rolando Paez Meireles under 37 C.F.R. § 1.132 (Oct. 8,
2011) (“Meireles Declaration”).
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teach or suggest a likelihood of success of treating diabetic foot ulcers
having a grade IV or V skin lesion by topically applying EGF encapsulated
in or associated with liposomes.” (Appeal Br. 4.) Appellants first argue that
the Meireles Declaration asserts Brown “would not lead one of ordinary []
skill in the art to have a reasonable expectation that topically administering
EGF in or associated to liposomes would be effective in treating advanced
diabetic foot ulcers for preventing diabetic foot amputation.” {Id. at 6.)
However, in support of this assertion the declaration merely states that
Brown cites to unpublished data in teaching that EGF accelerated epidermal
regeneration of chronic nonhealing diabetic ulcers. (Meireles Decl. | 5.)
We agree with the Examiner that there is no requirement data be published
in order to provide a reasonable expectation of success. (Ans. 11 .)n
Appellants further contend that Meireles Declaration asserts that
“Acosta arrived at [its] invention[] at least in part[] due to the fact that
topically administration of EGF consistently failed to solve the problem of
healing advanced diabetic foot ulcers,” that prior art such as Cohen “has
taught that the topical [] administration of growth factors failed to enhance
wound healing, even in human healthy volunteers bearing controlled acute
partial-thickness wounds,” and that “remaining references cited by the
11 Appellants additionally argue that Brown “conspicuously omits” diabetic
foot ulcers having a grade IV or V skin lesion from the list of wound models
that “provides additional evidence supporting the importance of prolonged
continuous exposure of the EGF to stimulate wound healing.” (Appeal Br.
4, 6 (citing Brown 793, first full paragraph).) We disagree with Appellants
that such omission without more is evidence that a skilled artisan “would not
believe that the topical administration of EGF to such wounds would be
effective.” {Id. at 6.) Under Appellants’ apparent logic, only an anticipatory
reference could invalidate a claim.
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[Ejxaminer relate to other technical fields and would not be looked to by
those skilled in the art for an improved treatment for complicated diabetic
foot ulcers.” (Appeal Br. 6.)
We are not persuaded. While Dr. Meireles asserts that Acosta applies
EGF intralesionally by injection and thus does not relate to topical
administration of EGF as claimed, “[n]on-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., 800 F.2d
1091, 1097 (Fed. Cir. 1986). Fikewise, Dr. Meireles does not cite to any
evidence in support of his opinion that Acosta arrived at its invention
because topically administered EGF failed to heal advanced diabetic foot
ulcers. (Meireles Decl. 1 6; see also Reply Br. 3.) Opinion evidence in
declarations, without factual support, are accorded little probative weight.
See In re Beattie, 974 F.2d 1309, 1313 (Fed. Cir. 1992).
We are similarly unconvinced by Dr. Meireles’ interpretation of
Cohen and Appellants’ arguments regarding that reference. Dr. Meireles
cites Cohen as “[t]he most illustrative example” of “studies [that] prove[d]
that topical administration of growth factors failed to enhance wound
healing” and that thus “calmed down the hyper-enthusiasm” for using
growth factors for wound healing in the field. (Meireles Decl. 17.)
As the Examiner points out, however, Cohen does not report the
amount of EGF used in the study and further suggests that the discrepancy
between its results and prior studies “may be due to the types of patients
used, types of wounds studied, and the presence of proteases and disease
states or processes.” (Ans. 12—13; FF28.) Thus, we do not agree that, in
light of Cohen, a skilled artisan would not have a reasonable expectation of
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success in treating diabetic foot ulcers with topically applied EGF.12 This is
particularly true given Acosta’s disclosure that injected EGF is useful in
treating such ulcers (FF7—9) and Brown’s disclosure that repeated topical
application of EGF or delivery of EGF in vehicles such as liposomes
enhanced wound healing (FF1—6.)
Appellants argue that the Examiner’s argument goes to the
“robustness of Cohen’s results” whereas Appellants are “merely relying
upon Cohen to demonstrate the state of mind of those skilled in the art.”
(Appeal Br. 7; Reply Br. 3.) We are not convinced. The limitations of
Cohen’s study, as set forth in the reference itself, are directly relevant to the
state of mind of those skilled in the art with respect to reasonable
expectation of success. Neither are we persuaded by Dr. Meireles’ claim
that subsequent to Cohen “no others described any beneficial effect of
topically delivered EGF to solve the problem of healing advanced diabetic
foot ulcers.” (Meireles Decl. 17.) Even assuming this claim to be true,
mere lack of an anticipatory reference does not suffice to show a lack of
reasonable expectation of success.
Finally, the Meireles Declaration asserts that Kaneko, Lundquist, and
Hinz relate to “other technical fields” and thus “have nothing to suggest to
someone looking for an improved treatment for complicated diabetic foot
ulcers.” {Id. at | 8.) While these three references are not related to
12 We note, but are not convinced by, Appellants’ argument that “if the
administration of EGF was unsuccessful when applied to partial-thickness
wounds in healthy volunteers, one skilled in the art most certainly would not
expect the topical administration of EGF to have positive results to a more
complicated clinical condition such as grade IV or V diabetic foot ulcers.”
(Reply Br. 4.) “Attorneys’ argument is no substitute for evidence.”
Johnston v. IVAC Corp., 885 F.2d 1574, 1581 (Fed. Cir. 1989).
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treatment of diabetic foot ulcers (FF10—16), we find that they are
“reasonably pertinent” to the problem with which Appellants are concerned
because they relate, among other things, to methods of drug delivery (FF11,
FF13, FF16). In any event, we do not find that these references are
necessary to provide a skilled artisan with a reasonable expectation of
success.
Accordingly, we affirm the Examiner’s rejection of claim 1 as
obvious over Brown, Acosta, Kaneko, Lundquist, and Hinz. Claims 2 and 3
have not been argued separately (Appeal Br. 8), and therefore fall with
claim 1. 37 C.F.R. § 41,37(c)(l)(iv).13
Appellants made no additional or different arguments with respect to
the Examiner’s rejection of claims 1 and 10 as obvious over Brown, Acosta,
Kaneko, Lundquist, Hinz, Cevc ’500, and Cevc Article. We therefore affirm
that rejection for the same reasons.
13 Appellants argue for the first time in the Reply Brief that Brown does not
disclose topically applying EGF because in Brown “[tjest solutions were
placed in the base of incisions, which were then closed with five evenly
placed interrupted horizontal mattress sutures” and thus were “applied deep
within the incision during surgery.” (Reply Br. 2—3, 4.) This argument is
untimely. See Ex parte Borden, 93 USPQ2d 1473, 1474 (BPAI
2010) (informative) (“The reply brief is not an opportunity to make
arguments that could have been made during prosecution, but were not. Nor
is the reply brief an opportunity to make arguments that could have been
made in the principal brief on appeal to rebut the Examiner's rejections, but
were not.”). In any event, this argument is unconvincing. Appellants do not
explain why applying test solution at the base of the wound (i.e., the
incision) would not fall within the broadest reasonable interpretation of
“topically administering” the solution. Furthermore, Bro wn provides other
disclosures relating to topical administration of EGF. (FF2, FF3.)
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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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