Ex Parte Baron et al

Patent Trial and Appeal Board

Apr 21, 2017

13423563 (P.T.A.B. Apr. 21, 2017)

United States Patent and Trademark Office
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O.Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
13/423,563 03/19/2012 Elma D. Baron CWR-021746US ORD 4863
68705 7590 04/25/2017
TAROLLI, SUNDHEIM, COVELL & TUMMINO, LLP
1300 EAST NINTH STREET
SUITE 1700
CLEVELAND, OH 44114
EXAMINER
BASQUILL, SEAN M
ART UNIT PAPER NUMBER
1613
NOTIFICATION DATE DELIVERY MODE
04/25/2017 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
rkline @ tarolli. com
docketing@tarolli.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ELMA D. BARON, KEVIN D. COOPER, MINH LAM,
PRANAB MUKHERJEE, MAHMOUD A. GHANNOUM,
and NANCY L. OLEINICK
Appeal 2016-004226
Application 13/423,5631
Technology Center 1600
Before ERIC B. GRIMES, JOHN G. NEW and DAVID COTTA,
Administrative Patent Judges.
COTTA, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
of photodynamic treatment of a fimgal infection in a subject in need thereof.
The Examiner rejected the claims on appeal under 35 U.S.C. § 103(a) as
obvious.
We AFFIRM.
1 According to Appellants, the real party in interest is Case Western Reserve
University. App. Br. 3.
Appeal 2016-004226
Application 13/423,563
STATEMENT OF THE CASE
Claims 1 and 3—17 are on appeal. Claim 1 below is illustrative and
reads as follows:
1. A method of photodynamic treatment of a fungal
infection in a subject in need thereof by administering
a therapeutically effective amount of a phthalocyanine
compound that has a structure according to formula I:
... or a pharmaceutically acceptable salt thereof to the
subject and activating the phthalocyanine with light.
Claim 1 also includes limitations requiring a number of specific
substituents, but those limitations are not relevant to the dispositive issues in
this appeal as Appellants do not dispute that the prior art compound Pc 4
encompasses the claimed substituents. In addition, we note that during
prosecution, in response to a restriction requirement requiring the election of
a species of phthalocyanine compound, Applicants elected the species Pc 4.
Response to Restriction Requirement p. 2 (filed Nov. 25, 2013).
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The claims stand rejected as follows:
Claims 1, 3—11, and 15 under 35 U.S.C. § 103(a) as unpatentable over
the combination of Baettig2 and Whitacre.3 Final Act.4 3 (“the First Ground
of Rejection”).
Claims 10-16 under 35 U.S.C. § 103(a) as unpatentable over the
combination of Baettig, Whitacre, Donnelly,5 and Piraccini.6 Final Act. 7
(“the Second Ground of Rejection”).
Claims 1 and 3—17 under 35 U.S.C. § 103(a) as unpatentable over the
combination of Baettig, Whitacre, Donnelly, Piraccini and Jori.7 Final Act.
8 (“the Third Ground of Rejection”).
FINDINGS OF FACT
1. Baettig discloses: “novel substituted, water soluble
phthalocyanine dyes, their salts, a method of their preparation and their use
in pharmaceutical compositions and medicaments for photodynamic therapy
[PDT] and for the treatment of infectious diseases induced by viruses, fungi
or microbes, cancer and dermatological diseases.” Baettig 11.
2 Baettig et al., US 2009/0155177 Al, published June 18, 2009 (“Baettig”).
3 Whitacre et al., Photodynamic Therapy with Phthalocyanine
Photosensitizer Pc4 of SW480 Human Colon Cancer Xenografts inAthymic
Mice, 6 Clinical Cancer Research, 2021-2027 (2000) (“Whitacre”).
4 Office Action mailed Jan. 27, 2015.
5 Donnelly et al., Bioadhesive Patch-Based Deliver of 5-Aminolevulinic
Acid to the Nail for Photodynamic Therapy of Oncychomycosis, 103 J. OF
Controlled Release, 381-92 (2005) (“Donnelly”).
6 Piraccini et al., Photodynamic Therapy of Onychomycosis Caused by
Trichiphyton Rubrum, 59 J. Am. Acad. Dermatol. 875—76 (2008)
(“Piraccini”).
7 Jori et al., Photodynamic Therapy in the Treatment of Microbial
Infections: Basic Principles and Perspective Applications, 3 8 Lasers in
Surgery and Medicine, 468-481 (2006) (“Jori”).
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Application 13/423,563
2. Baettig discloses:
Photodynamic therapy is a method for treatment of tumors and
other tissue alterations by light in combination with a light
sensitive substance, a so-called photosensitizer, and oxygen
contained in the tissue. Such a sensitizer or one of its metabolic
precursors is administered to a patient. This sensitizer or
metabolic precursor selectively accumulates in the tumor. After
a certain waiting time, the tumor and the surrounding healthy
tissue are irradiated with light of an appropriate wavelength.
Photophysical processes generate toxic substances, so-called
reactive oxygen species, from oxygen contained in the tissue.
These reactive oxygen species selectively damage the tumor,
because the sensitizer has selectively accumulated in the tumor
tissue.
Id. at 12.
3. Baettig discloses:
Optimal wavelengths for photodynamic therapy are situated
between 600 nm and 1500 nm. At shorter wavelengths, the
tissue is not transparent enough for the radiation and at longer
wavelengths the energy of the radiation is too low. The
penetration depth in tissue is 4 mm at a wavelength of 630 nm
and 8 mm at a wavelength of 700 nm.
Id. at 19.
4. Baettig discloses: “There is therefore still a need for improved
photosensitizers for photodynamic therapy having these properties. In
particular, the absorption maximum of the compounds should be above 630
nm, preferably above 650 nm.” Id. at 118. Baettig further discloses that
“[t]he phthalocyanine dyes according to the invention may be activated by
light having a wavelength above about 670 nm, which penetrates quite easily
into the body tissue.” Id. at 148.
5. Whitacre discloses: “Photodynamic therapy (PDT) using the
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Application 13/423,563
silicon phthalocyanine photosensitizer Pc 4 ... is an oxidative stress
associated with induction of apoptosis in various cell types.” Whitacre
Abstract.
6. Whitacre discloses:
PDT is a novel mode of cancer treatment in which visible light
of an appropriate wavelength activates a tumor-associated
photosensitizer to produce reactive oxygen. . . . PDT causes lipid
peroxidation and damage to multiple cellular sites, including
membranes, DNA, and cytoskeleton, followed by apoptosis in
some cell lines and apoptosis and rapid regression of solid
tumors.
Id. at 2021 (internal citations omitted).
7. Whitacre discloses:
Pc 4 was delivered via tail vein injection, and 48 h later a 1-cm-
diameter area encompassing the tumor was irradiated (power
density, 150 mW/cm2; X, 670 ± 1 nm; fluence, 150 J/cm2 with
light from a 250-mW diode laser (Applied Optronics Corp.,
South Plainfield, NJ) coupled to a 400-pm quartz fiber-optic
cable terminating in a microlens to distribute light uniformly
throughout the treatment field.
Id. at 2022.
8. Whitacre discloses: “Pc 4-PDT is effective in the treatment of
SW480 human colon cancer xenografts independent of p53 status.” Id. at
Abstract.
9. Donnelly discloses: “Recently, the use of PDT, based on
topical application of 5-aminolevulinic acid (ALA), has been extended from
the oncological field to that of antimicrobial chemotherapy. ALA
administration has been shown to induce accumulation of the photosensitiser
protoporphyrin IX (PpIX) in, and allow subsequent photodynamic
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destruction of, bacteria and fungi.” Donnelly 382 (internal citations
omitted).
10. Piraccini discloses: “The use of PDT has been recently
extended from the oncologic field to that of antimicrobial chemotherapy. In
vitro studies have demonstrated that fungi can be effectively photosensitized
after topical delivery of 5-aminolevulinic acid and killed at dose rates much
lower than those that kill keratinocytes.” Piraccini 875.
11. Jori discloses: “PDT appears to represent an efficacious
alternative modality for the treatment of localized microbial infections
through the in situ application of the photosensitizer followed by irradiation
of the photosensitizer-loaded infected area.” Jori 468.
THE FIRST GROUND OF REJECTION
Appellants argue claims 1, 3—11, and 15 together as a group. We
designate claim 1 as representative of the group.
In rejecting claims 1, 3—11, and 15 under 35 U.S.C. § 103(a) as
obvious, the Examiner found that Baettig disclosed the photodynamic
treatment of fungal infections using phthalocyanine dyes as photosensitizers,
but did not disclose photodynamic treatment using the elected Pc 4
compound. Ans. 2. The Examiner found that Whitacre taught that Pc 4 was
an “alternative phthalocyanine PDT photosensitizing agent commercially
available at the time of the instant invention having an extinction wavelength
of 670+1 nm.” Id.
Based on the combined teachings of Baettig and Whitacre, the
Examiner concluded:
It would have been prima facie obvious for a skilled artisan at
the time of the instant invention to have used the alternative
phthalocyanine PDT photosensitizing agent PC4 as the
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phthalocyanine PDT photosensitizing agent in the method of
treating fungal infection disclosed by Baettig. One having
ordinary skill in the art would have been motivated to do so
owing to the known utility of PC4 as a phthalocyanine PDT
photosensitizing agent having an extinction wavelength of 670
as required by the preferred embodiments of phthalocyanine
PDT photosensitizing agents disclosed by Baettig. The choice
of employing PC4 as the PDT photosensitizer therefore
amounts to little more than the selection of a known material
for use in a method of treatment, based on its recognized
suitability for its intended use.
Id. at 2—3. We agree with and adopt the Examiner’s findings and reasoning,
and agree that claim 1 would have been obvious based on the Baettig and
Whitacre. We address Appellant’s arguments below.
Appellants argue that Baettig does not provide an enabling disclosure
for treatment of fungal infection using phthalocyanine dyes as
photosensitizers. According to Appellants, Baettig discloses no more than
“a brief statement that their phthalocyanine dyes can be used for ‘treatment
of viral, fungal or bacterial infection diseases, cancer and dermatological
diseases.’” App. Br. 8. Baettig does not provide examples or specify
species of fungus that can be treated. Instead, Appellants argue, “Baettig
focuses primarily on cancer treatment and methods for synthesizing their
novel phthalocyanine dyes.” Id. Appellants further argue that the absence
of an enabling disclosure is demonstrated by the prosecution history of
Baettig, in which “claims reciting the treatment of viral, fungal or bacterial
infection were rejected under 35 USC 112, 1st paragraph for lack of
enablement.” Id. We are not persuaded.
As an initial matter, the Examiner’s rejection of the Baettig patent
application for lack of enablement is not dispositive with respect to whether
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Baettig enables the treatment of fungal infections using phthalocyanine dyes.
Not only was the record belbre the Examiner during the Baettig prosecution
different from the record currently before us, but the scope of the rejected
claims in Baettig was considerably broader than the scope of the teachings
relied upon by the Examiner in finding Appellants’ claim 1 obvious. See,
Office Action (Application No. 12/316,840) mailed February 19, 2010, p. 2
(“The claims [of the Baettig application] are interpreted to include any and
all forms of viral, fungal and bacterial infections, dermatological diseases
and cancer. In light of this, it can be asserted that in spite of the vast
expenditure of human and capital resources in recent years, no one drug has
been found which is effective in treating all types of cancer because it is not
a simple disease, nor is it even a single disease, but a complex of a multitude
of different entities, each behaving in a different way.”).
While the Examiner’s findings in connection with the Baettig
prosecution are not dispositive, we have nonetheless considered the findings
in the Baettig non-enablement rejection together with the arguments raised
by Appellants. We are not persuaded that the skilled artisan would have
required undue experimentation in order to treat fungal infection using
phthalocyanine dyes as photosensitizers as taught in Baettig.
The record reflects that, at the time of the invention, it was well
known that photosensitizers could be used to treat fungal infections. See
FF9--FFI1; see also, App. Br. 10 (Conceding that it was known that “fungal
infections could be treated by photodynamic therapy using certain known
compounds.”). Neither Appellants nor the enablement rejection in the
Baettig prosecution identifies any objective evidence establishing that the
skilled artisan would require undue experimentation in order to apply the
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teaching of the use of Baettig’s phthalocyanine compounds to treat fungal
infection. Indeed, in connection with the claimed phthalocyanine
compound, the Specification teaches: “Dosage amounts and preferred
formulations can be readily established by reference to known treatment or
prevention regimes/'’ Spec. 1j 39. We expect that a skilled artisan would
similarly be able to “readily establish” dosage amounts and preferred
formulations with respect to Baettig’s phthalocyanine compounds.
Appellants have not introduced persuasive evidence to the contrary .
Appellants argue that the fact that the absorption wavelength of Pc 4
is the same as a preferred absorption wavelength of the phthalocyanine dyes
of Baettig does not render the claims obvious because “the absorption
wavelength is only one of several factors required [to be] effective for use as
an antifungal agent, which is the relevant use.” App. Br. 11—12. Appellants
further argue that the compounds of Baettig have “signi ficant structural
differences from PC4” and that because of these differences, the substitution
of Pc 4 for the phthalocyanine dyes of Baettig “does not represent selection
of a known material for use in a method of treatment based on recognized
suitability for intended use.” Id. at 13. Appellants also assert that Baettig
“teach[es] away from the use of phthalocyanine compounds such as PC4 that
lack the key ary! groups.” Id. at 14. We are not persuaded,
Baettig discloses phthalocyanine dyes that can be used as
photosensitizers in photodynamic therapy for the treatment of infectious
diseases induced by viruses, fungi or microbes, cancer and dermatological
diseases. FF1. Baettig teaches that in photodynamic therapy, a
photosensitizer accumulates at the target site and is irradiated with light of a
certain wavelength. FF2. This generates “toxic substances, so-called
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reactive oxygen species, from oxygen contained in the tissue.” Id. Baettig
further teaches that optimal photosensitizers have an absorption maximum
“above 630 nm, preferably above 650 nm” and that the penetration depth of
irradiation “is 4 mm at a wavelength of 630 nm and 8 mm at a wavelength of
700 nm.” FF3 and FF4. Baettig’s phthalocyanine dyes are activated by light
having a wavelength of 670 nm. FF4.
Whitacre discloses a species of phthalocyanine photosensitizer — Pc 4
— that has an excitation wavelength of 670 nm. FF7. Consistent with
Baettig’s teachings, Whitacre teaches that in photodynamic therapy “light of
an appropriate wavelength activates a tumor-associated photosensitizer to
produce reactive oxygen.” FF6. While Whitacre does not specifically
disclose that Pc 4 can be used to treat fungal infection, it does teach that
photodynamic therapy with Pc 4 creates “oxidative stress associated with
induction of apoptosis in various cell types,” (FF5), and that Pc 4 is effective
in treating tumors. FF8.
Given that both Pc 4 and Baettig’s phthalocyanine dyes are
photosensitizers that generate reactive oxygen species upon excitation with
light of the same wavelength, that Baettig teaches that its phthalocyanine
dyes can be used to treat fungal infections, and that Whitacre teaches that
PDT therapy with Pc 4 is associated with induction of apoptosis, we find
that the skilled artisan would have found it obvious to use Pc 4 to treat
fungal infections.
Accordingly, we affirm the Examiner’s decision to reject claims 1, 3—
11, and 15 under 35 U.S.C. § 103(a) as unpatentable over the combination of
Baettig and Whitacre.
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THE SECOND GROUND OF REJECTION
Claims 10—16 depend, directly or indirectly, from claim 1 and further
specify the type of fungus (claims 10-12), the type of fungal infection
treated (claims 13 and 14), the subject to be treated (claim 15) and the
manner of administration (claim 16). The Examiner found that Donnelly
and Piraccini disclosed these elements in connection with the use of the
photosensitizing compound 5-aminolevulinic acid (“5-ALA”). The
Examiner concluded that it would have been obvious to use Pc 4 as recited
in claims 10—16 given the “acknowledged utility of PDT in the treatment of
fungal infections and onychomycosis caused by either of Candida albicans
or Trichophyton rubrum, [a]s well as the acknowledged utility of PC4 to act
as a photosensitizing agent useful in treating fungal infections.” Ans. 4.
The Examiner reasoned that “[t]he choice of employing PC4 as the PDT
photosensitizer in the treatment of these fungal infections . . . amounts to
little more than the selection of a known material for use in a method of
treatment, based on its recognized suitability for its intended use.” Id. We
agree with and adopt the Examiner’s findings and reasoning, and agree that
claims 10-16 would have been obvious based on the cited art. We address
Appellant’s arguments below.
Appellants argue that 5-ALA, as disclosed in Donnelly and Piraccini,
is “a different class of compound than phthalocyanines, and as a result
exhibits substantial differences, such as localization in mitochondria, unlike
PC4 which localizes in the parenchyma.” App. Br. 15 (citing Whitacre et
al., p. 2022). Accordingly, Appellants argue, “it would not have been
obvious that PC4 could be substituted for the photosensitizer 5-ALA.” Id. at
15.
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We are not persuaded. We find that the skilled artisan would have
considered the teachings of Donnelly and Piraccini’s with respect to 5-ALA
to be applicable to Pc 4, notwithstanding any differences in structure,
because 5-ALA and Pc 4 are photosensitizers that were known to be useful
or would have been expected to be useful for the treatment of fungal
infections and because photosensitizers operate in the same manner — by
generating reactive oxygen species. FF2 and FF6.
Accordingly, we affirm the Examiner’s decision to reject claims 10-
16 under 35 U.S.C. § 103(a) as unpatentable over the combination of
Baettig, Whitacre, Donnelly and Piraccini.
THE THIRD GROUND OF REJECTION
Claim 17 depends from claim 1 and further specifies that the
phthalocyanine compound is “administered in a pharmaceutical carrier and
has a concentration from about 0.05 mg/ml to about 0.1 mg/ml.” The
Examiner found that this element was disclosed in Jori and thus found claim
17 obvious over the combination of Baettig, Whitacre, Donnelly, Piraccini
and Jori.8 Ans. 5. Appellants discuss the Jori reference, but do not present
persuasive argument or evidence that the claimed concentration would not
have been obvious. See, App. Br. 10 and 12.
Accordingly, we affirm the Examiner’s decision to reject claims 1
and 3—17 under 35 U.S.C. § 103(a) as unpatentable over the combination of
Baettig, Whitacre, Donnelly, Piraccini and Jori.
The Examiner also applied this ground of rejection to claims 1 and 3—16.
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SUMMARY
For the reasons provided herein and those set forth in the Examiner's
Answer and the Final Office Action, the Examiner’s decision to reject
claims 1 and 3—17 under 35 U.S.C. § 103(a) as obvious 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)(1).
AFFIRMED
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