Ex Parte Leveugle

Patent Trial and Appeal Board

Dec 21, 2012

10470519 (P.T.A.B. Dec. 21, 2012)

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.
10/470,519 02/04/2004 Beatrice Leveugle 2483QPI-1 8433
22442 7590 12/21/2012
Sheridan Ross PC
1560 Broadway
Suite 1200
Denver, CO 80202
EXAMINER
RAMACHANDRAN, UMAMAHESWARI
ART UNIT PAPER NUMBER
1627
MAIL DATE DELIVERY MODE
12/21/2012 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 BEATRICE LEVEUGLE
__________

Appeal 2011-011754
Application 10/470,519
Technology Center 1600
__________

Before ERIC GRIMES, FRANCISCO C. PRATS, and STEPHEN WALSH,
Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to methods
of treating cancer. The Examiner has rejected the claims as obvious. We
have jurisdiction under 35 U.S.C. § 6(b). We affirm but designate the
affirmances as new grounds of rejection.
STATEMENT OF THE CASE
The Specification discloses “photodynamic therapy (PDT) and
sonodynamic therapy (SDT) … for the treatment of cancer. These therapies
involve systemic or topical administration of a sensitizer, followed by its
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activation by light of a specific wavelength (PDT), or activation by sound of
a specific frequency (SDT).” (Spec. 2:18-22.)
Claims 1, 2, 3, 5, 8, 13 and 14 are on appeal. Claim 1, the only
independent claim, reads as follows:
1. A method of potentiating activity of an administered
immunotherapeutic agent in cancer therapy comprising
a) administering a composition comprising a hypocrellin derivative
consisting of a compound selected from the group consisting of
butylaminatedhypocrellin B; 2-(N,N-dimethylamino)-propylamine-
hypocrellin B; ethanolaminated hypocrellin B; and 1,12-Bis[2-
(acetyloxy)propyl]-2,4,6,7,9,11-hexamethoxy-3,10-perylenedione,
compounds of the formulae

and

and wherein R1, R2, R3, R4 are OCH3 or NHCH2Ar (Ar are phenyl or pyridyl
group), NHCH(CH2)n (wherein -CH(CH2) are alicyclic groups and
n=3,4,5,6), said hypocrellin derivative being a sonosensitizer and/or a
photosensitizer, and
b) activating the hypocrellin derivative, wherein said activation is
effected by light or sound or by light and sound; and
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c) separately administering the immunotherapeutic agent comprising
an antibody that is not conjugated to the hypocrellin derivative of step a)
after administering the hypocrellin composition of step a) and activating the
hypocrellin in step b).

The claims stand rejected under 35 U.S.C. § 103(a) as follows:
• Claims 1, 3, 5, 8 and 13 in view of Fanslow1 and Wu;2
• Claim 2 in view of Fanslow, Wu and Iger;3 and
• Claim 14 in view of Fanslow, Wu and Eccles.4
I.
Issue
The Examiner has rejected claims 1, 3, 5, 8 and 13 as obvious in view
of Fanslow and Wu, and has rejected claim 2 as obvious in view of Fanslow,
Wu, and Iger. We will consider the rejections together since Appellant has
waived any argument based on Iger (Appeal Br. 14-15).
The Examiner finds that Fanslow discloses treating cancer with a
“CD40 binding protein in conjunction with photodynamic therapy [PDT],”
where the CD40 binding protein can be an antibody to CD40 (Answer 5).
The Examiner finds that Fanslow discloses that “combining PDT with … a
CD40 binding protein should significantly enhance the in vivo anti-tumor
immune response” (id.). The Examiner finds that Fanslow’s Example 2

1 Fanslow III et al., US 2002/0041864 A1, Apr. 11, 2002.
2 Wu et al., New potential photodynamic therapeutic anti-cancer agents:
synthesis and characterization of demethoxy amino-substituted hypocrellins,
15 ANTI-CANCER DRUG DESIGN 287-293 (2000).
3 Iger, WO 98/52610, Nov. 26, 1998.
4 Eccles, Monoclonal antibodies targeting cancer: ‘magic bullets’ or just the
trigger?, 3 BREAST CANCER RESEARCH 86-90 (2001).
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discloses the “administration of a photosensitizing compound followed by
activation” by light and subsequent administration of a CD40 binding
protein (id.).
The Examiner finds that Fanslow does not teach hypocrellin
compounds (id. at 6), but Wu discloses “demethoxy amino-substituted
hypocrellins … [having] photodynamic therapy advantages over commonly
used photofrins” (id.). The Examiner finds that Wu discloses that its
“compound 3 exhibited much greater phototoxicity than the[ ] parent
hypocrellins and … qualifies as a better photodynamic therapeutic agent”
(id.). The Examiner concludes that it “would have been obvious to one of
ordinary skill in the art … to administer hypocrellin as a photosensitizer in
Fanslow’s method of treating tumors … because the claimed hypocrellin
compounds are taught by Wu as photosensitizing compounds for treating
cancer” (id.).
Appellant contends that Fanslow’s Example 1 teaches away from the
claimed invention and Fanslow’s Example 2 is a prophetic example (Appeal
Br. 11-13). Appellant also argues that Wu only tested one demethoxy
amino-substituted hypocrellin and that Wu “does not teach one of skill in the
art that all demethoxy amino-substituted hypocrellins will demonstrate much
greater phototoxicity than the parent hypocrellins A and B” (id. at 13-14).
The issue presented is: Does the evidence of record support the
Examiner’s conclusion that the cited references would have made obvious
the method of potentiating the activity of an administered immuno-
therapeutic agent in cancer therapy that is defined by claim 1?
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Findings of Fact
1. Fanslow discloses that “[p]hotodynamic therapy (PDT) is a
treatment for cancer that involves the use of a photosensitizer and light”
(Fanslow 1, ¶ 0002).
2. Fanslow discloses that cancerous cells “retain the photosensitizer
more readily than normal tissues. Subsequent exposure of the cells to
wavelength-specific light induces a photochemical reaction that causes
oxidative damage to numerous cellular components and cell death.” (Id.)
3. Fanslow discloses a “method for inducing a memory cytotoxic T
lymphocyte (CTL) response in a tumor-bearing subject comprising
administering a therapeutically effective amount of a CD40 binding protein
to said subject in combination with photodynamic therapy” (id. at 1, ¶ 0008).
4. Fanslow discloses that a “variety of CD40 binding proteins may be
employed …, including, for example, an antibody that binds CD40” or
CD40 ligand (id. at 1, ¶ 0011).
5. Fanslow discloses that the “particular photosensitizer employed is
not crucial to the present invention.… A preferred photosensitizer employed
is Photofrin®.” (Id. at 4, ¶ 0044.)
6. Fanslow discloses that “[c]ombining PDT with administration of a
CD40 binding protein should significantly enhance the in vivo anti-tumor
immune response” (id. at 6, ¶ 0064).
7. Fanslow’s Example 2 is a prophetic example that describes the
administration of a CD40 binding protein to tumor-bearing subjects after
PDT, and states that the combination “enhances anti-tumor treatment” (id. at
6, ¶ 0065).
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8. Wu discloses “potential photodynamic therapeutic anti-cancer
agents” (Wu 287, title).
9. Wu discloses that hypocrellin A (HA) and hypocrellin B (HB)
exhibit “several advantages over the presently used photodynamic
therapeutic (PDT) agent photofrin” (id. at 287, left col.).
10. Wu discloses that “as in the case of photofrin, hypocrellins do not
exhibit absorptivity at >600 nm sufficiently strong for photodynamic
therapy, and this has limited their PDT applications to date” (id. at 287, left–
right col.).
11. Wu discloses “demethoxy amino-substituted hypocrellin
derivatives (AHDs) which demonstrate significantly enhanced red
absorptivity (>600 nm) and strong active oxygen … generating properties”
(id. at 287, right col.).
12. Wu’s compound 3 is shown below:

Wu discloses that compound 3 is “2-butylamino demethoxy HB,” and “3
consists of two tautomers – a ketone form (3a) and an enol form (3b)” (id. at
289, right col.).
13. Wu discloses that “[c]ompound 3 exhibited much greater
phototoxicity than their parent hypocrellins … which qualifies 3 as a better
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photodynamic therapeutic anti-cancer agent than the parent hypocrellins”
(id. at 292, right col.).
Analysis
Claim 1 is directed to a method comprising administering a
composition comprising one of a set of specified hypocrellin derivatives,
activating the hypocrellin derivative by light or sound, and then
administering an immunotherapeutic antibody.
Fanslow discloses treating cancer using a combination of
photodynamic therapy (PDT) and administration of a CD40 binding protein,
such as an antibody that binds CD40. Fanslow discloses that a preferred
photosensitizer is Photofrin® and that the combination therapy should
significantly enhance the anti-tumor immune response.
Wu discloses that hypocrellins A and B have advantages over
photofrin in PDT but none of the three compounds exhibit sufficient
absorptivity at >600 nm. Wu discloses hypocrellin derivatives with
enhanced absorptivity at wavelengths >600 nm and strong active oxygen
generating properties. Wu discloses that its compound 3 (2-butylamino
demethoxy hypocrellin B) exhibited much greater phototoxicity than
hypocrellins A and B and is therefore a better PDT agent. In view of these
disclosures, it would have been obvious to one of ordinary skill in the art to
modify Fanslow’s method of administering PDT followed by anti-CD40
antibody by using Wu’s compound 3 as a photosensitizer because Wu
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suggests that compound 3 would have advantages over photofrin in anti-
cancer therapy.5
Appellant argues that Fanslow’s Example 1 teaches away from using
an antibody because it “shows that the administration of an antibody in
combination with photodynamic therapy results in no change in the effect of
PDT (see, control rat [I]gG), or an elimination of the effect of PDT (anti-
CD40 ligand antibody). Thus … the antibodies used therein in combination
with PDT do not improve the anti-tumor immune response.” (Appeal Br.
12).
This argument is not persuasive. As discussed above, Fanslow
expressly suggests the use of PDT in combination with an antibody that
binds and activates CD40. As Appellant acknowledges (Appeal Br. 12), the
antibodies used in Fanslow’s Example 1 were a rat IgG used as a negative
control, which was not expected to bind to anything, and an antibody that
binds CD40 ligand, thus inhibiting activation of CD40. These antibodies are
different from the anti-CD40 antibody that Fanslow suggests combining
with PDT for cancer treatment.
Appellant also argues that Fanslow’s Example 2 is a prophetic
example (Appeal Br. 11). Appellant argues that although Fanslow “recites
the steps of an anti-cancer treatment combining PDT with immunotherapy in

55 Wu’s compound 3 (2-butylamino demethoxy hypocrellin B) corresponds
to the second formula recited in claim 1, where R1, R2, and R4 are OCH3 and
R3 is NHCH(CH2)n where n=3. Cf. Spec. 13:1-2 (“A hypocrellin derivative
of the present invention also includes 2-butylamino-2-demethoxy-
hypocrellin B (2-BA-2-DMHB)”) and 9:2-3 (“2-BA-2-DMHB is where R1,
R2, R3 are OCH3, and R4 is NH(CH2)3CH3”).
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Example 2, there is no indication that such combined therapy was in any
way successful or even promising” (id. at 13). Appellant argues that the
procedures in Fanslow’s Example 2 “are merely a wish list of experimental
protocols that could be utilized.… Such wish list is certainly insufficient to
support an inference that one of skill in the art would regard such therapy as
useful or efficacious.” (Id.)
This argument is also unpersuasive. Fanslow expressly discloses that
“[c]ombining PDT with administration of a CD40 binding protein should
significantly enhance the in vivo anti-tumor immune response” (FF 6) and
that a CD40 binding antibody is a suitable CD40 binding protein (FF 4).
“[A] presumption arises that both the claimed and unclaimed disclosures in a
prior art patent are enabled.” Amgen, Inc. v. Hoechst Marion Roussel, Inc.,
314 F.3d 1313, 1355 (Fed. Cir. 2003).
Appellant has not provided any evidence that Fanslow does not enable
providing an anti-tumor treatment using PDT therapy in combination with
anti-CD40 antibodies. Nor has Appellant provided evidence or sound
reasoning to show that a skilled worker would not have expected Fanslow’s
treatment method to be effective, notwithstanding the fact that Fanslow did
not actually carry out the treatment in vivo. See In re Kumar, 418 F.3d
1361, 1368 (Fed. Cir. 2005) (Patent applicants bear the burden of
“presenting sufficient reason or authority or evidence, on the facts of the
case, to show that the prior art method would not produce or would not be
expected to produce the claimed subject matter.”).
Appellant also argues that Wu only tested one demethoxy amino-
substituted hypocrellin and “does not teach … that all demethoxy amino-
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substituted hypocrellins will demonstrate much greater phototoxicity than
the parent hypocrellins A and B” (Appeal Br. 13-14). This argument is not
persuasive since the Wu’s compound 3 is within the scope of claim 1 and is
disclosed to have greater phototoxicity than the parent hypocrellins.
Appellant argues that the Examiner erred in finding that Wu’s
compound 3 is the same as the compound recited in dependent claim 8
(Appeal Br. 14), and Wu “does not teach one of skill in the art that all
demethoxy amino-substituted hypocrellins will demonstrate much greater
phototoxicity than the parent hypocrellins A and B” (id.).
In response to Appellant’s arguments, the Examiner acknowledged
that Wu’s compound 3 is not the same as the compound recited in claim 8
(Answer 12-13). Specifically, claim 8 requires that R1, R2, and R3 are OCH3
and R4 is NH(CH2)3CH3, but in Wu’s compound 3, R1, R2, and R4 are OCH3
and R3 is NH(CH2)3CH3. The Examiner concludes, however, that the
compound of claim 8 would have been obvious based on the hypocrellin
derivatives disclosed by Wu, because Wu “teaches butyl amino demethoxy
compounds of Hyp A [HA] and Hyp B [HA] … as photodynamic
therapeutic anti-cancer agents” (id. at 13).
We agree with the Examiner's reasoning and conclusion set forth in
the Answer (pages 13-14). That is, the compound recited in claim 8 is the
same as Wu’s compound 3 except with the R3 and R4 substituents switched
around, and the Examiner concludes that the compound of claim 8 would
have been obvious based on Wu’s very similar compound. Appellant has
provided no evidence or sound reasoning to support a contrary conclusion.
Simply pointing out a difference between a claimed compound and the prior
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art is not a sufficient basis for concluding that the claimed compound would
not have been obvious based on the prior art.
Thus, we affirm the rejection of claims 1 and 8 as obvious in view of
Fanslow and Wu. Claims 3, 5, and 13 were not argued separately and
therefore fall with claim 1. 37 C.F.R. § 41.37(c)(1)(vii). We also affirm the
rejection of claim 2 as obvious in view of Fanslow, Wu and Iger, since
Appellant has waived any argument based on Iger (Appeal Br. 14-15).
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that the
cited references would have made obvious the claimed method of
potentiating the activity of an administered immunotherapeutic agent in
cancer therapy.
II.
Issue
The Examiner has rejected claim 14 as obvious in view of Fanslow,
Wu, and Eccles. Claim 14 is directed to the method of claim 1, “wherein the
antibody is a tumor specific antibody” (Appeal Br. 18 (Claims Appendix)).
The Examiner relies on Fanslow and Wu as discussed above (Answer
8). The Examiner finds that Eccles discusses “monoclonal antibodies
approved for cancer therapy clinical trials to specifically target the cancer
cells, for example, … herceptin for metastatic breast cancer” (id. at 9). The
Examiner concludes that it “would have been obvious to one having
ordinary skill in the art … to administer a tumor specific antibody in treating
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cancer after PDT therapy because with tumor specific antibodies, specific
tumors or cancers can be effectively targeted as taught by Eccles” (id.).
Appellant contends that Eccles does not disclose or suggest that “there
is a known mechanism of action or biological reason to expect that the
antibodies described would be effective in combination with PDT therapy”
(Appeal Br. 15).
The issue with respect to this rejection is: Does the evidence of
record support the Examiner’s conclusion that the cited references would
have made obvious the use of Eccles’ anti-tumor antibodies in the therapy
method suggested by Fanslow and Wu?
Additional Findings of Fact
14. Eccles discloses that Herceptin® [anti-(c-erbB-2/HER-2)] has
received regulatory approval for treatment of metastatic breast cancer
(Eccles 86).
15. Fanslow discloses that “the combination of a CD40 binding
protein and PDT may be supplemented by the use of additional active
agents” (Fanslow 5, ¶0055).
16. Fanslow discloses that its combination treatment “may be used in
conjunction with other therapies appropriate for afflicted subjects, including
chemotherapy, radiation therapy, and immunotherapy” (id. at 6, ¶0060).
Analysis
Fanslow and Wu are discussed above. Eccles discloses that
Herceptin® [anti-(c-erbB-2/HER-2)] has been approved by the FDA for the
treatment of metastatic breast cancer. In view of this disclosure, it would
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have been obvious to modify the PDT therapy method suggested by Fanslow
and Wu (i.e., PDT therapy with a CD40 binding agent) to include treatment
with the Herceptin® antibody disclosed by Eccles in the treatment for
metastatic breast cancer because Fanslow expressly suggests combining its
treatment method with immunotherapy.
Appellant contends that “Eccles would not teach one of skill in the art
that there is a known mechanism of action or biological reason to expect that
the antibodies described would be effective in combination with PDT
therapy” (Appeal Br. 15).
This argument is not persuasive. Eccles discloses that the anti-tumor
antibody Herceptin® has been approved for the treatment of metastatic
breast cancer. Fanslow and Wu disclose that PDT therapy has been shown
to be effective in targeting cancer cells. Even if the exact mechanism of
action for anti-tumor antibodies has not been established, one of ordinary
skill in the art would expect that combining two successful treatment
methods would improve the effect compared to either method used alone.
Appellant has not pointed to anything in Eccles to suggest that the treatment
with Herceptin would interfere with Fanslow’s treatment method or vice
versa.
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that the
cited references would have made obvious the use of Eccles’ anti-tumor
antibodies in the therapy method suggested by Fanslow and Wu.
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SUMMARY
We affirm the rejections under 35 U.S.C. § 103(a) of claims 1, 3, 5, 8,
and 13 in view of Fanslow and Wu, claim 2 in view of Fanslow, Wu, and
Iger, and claim 14 in view of Fanslow, Wu, and Eccles. However, since our
reasoning differs from, or at least expands significantly on, the Examiner’s
reasoning, we designate the affirmances as new grounds of rejection in order
to provide Appellant a fair opportunity to respond.
TIME PERIOD FOR RESPONSE
This decision contains a new ground of rejection pursuant to 37 CFR
§ 41.50(b) (effective September 13, 2004, 69 Fed. Reg. 49960 (August 12,
2004), 1286 Off. Gaz. Pat. Office 21 (September 7, 2004)). 37 CFR
§ 41.50(b) provides “[a] new ground of rejection pursuant to this paragraph
shall not be considered final for judicial review.
37 CFR § 41.50(b) also provides that the Appellant, WITHIN TWO
MONTHS FROM THE DATE OF THE DECISION, must exercise one of
the following two options with respect to the new ground of rejection to
avoid termination of the appeal as to the rejected claims:
(1) Reopen prosecution. Submit an appropriate
amendment of the claims so rejected or new evidence relating
to the claims so rejected, or both, and have the matter
reconsidered by the examiner, in which event the proceeding
will be remanded to the examiner ….

(2) Request rehearing. Request that the proceeding be
reheard under § 41.52 by the Board upon the same record ….

AFFIRMED/37 C.F.R. § 41.50(b)

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