Ex Parte Hart et al

Patent Trial and Appeal Board

Jun 18, 2018

13809135 (P.T.A.B. Jun. 18, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
13/809, 135 07/24/2013 Charles Hart
134576 7590 06/20/2018
FOLEY & LARDNER LLP
3000 K STREET N.W.
SUITE 600
WASHINGTON, DC 20007-5109
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.
095401-0353 8006
EXAMINER
RODRIGUEZ, RAYNA B
ART UNIT PAPER NUMBER
1628
NOTIFICATION DATE DELIVERY MODE
06/20/2018 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):
ipdocketing@foley.com
mhopkins@thresholdpharm.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte CHARLES HART, JOHN CURD, STEWART KROLL,
and JESSICA SUN
Appeal2016-008592
Application 13/809, 135 1
Technology Center 1600
Before DONALD E. ADAMS, ULRIKE W. JENKS and DAVID COTTA,
Administrative Patent Judges.
COTT A, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
of treating a cancer patient. The Examiner rejected the claims on appeal
under 35 U.S.C. § 102(b) as anticipated and under 35 U.S.C. § 103(a) as
obvious.
We affirm.
1 According to Appellants, the real party in interest is Threshold
Pharmaceuticals, Inc. Br. 2.
Appeal 2016-008592
Application 13/809, 135
STATEMENT OF THE CASE
Claims 1-3, 5-8 and 15 are on appeal. Claim 1 is illustrative and
reads as follows:
1. A method of treating a cancer patient in need of such
treatment, said method compnsmg administering an
antiangiogenic agent and administering a hypoxia activated
prodrug that is TH-302 to said patient, wherein the hypoxia
activated prodrug is administered once weekly.
App. Br. 8. In response to a restriction requirement, Appellant elected
bevacizumab as the claimed antiangiogenic agent, TH-302 as the claimed
hypoxia activated prodrug, and glioblastoma as the claimed cancer.
Response to Restriction Requirement, mailed July 3, 2014 at 4.
The claims stand rejected as follows.
Claims 1 and 5-8 were rejected under 35 U.S.C. § 102(b) as
anticipated by Matteucci. 2
Claim 3 was rejected under 35 U.S.C. ,r 103(a) as obvious over
Matteucci.
Claims 2 and 15 were rejected under 35 U.S.C. ,r 103(a) as obvious
over the combination of Matteucci and Duan. 3
Claims 1 and 5-8 were rejected under 35 U.S.C. ,r 103(a) as obvious
over the combination of Matteucci and Friedman. 4
2 Mark Matteucci et al., WO 2007 /002931 A2, published Jan. 4, 2007
("Matteucci").
3 Jian-Xin Duan et al., Potent and Highly Selective Hypoxia-Activated
Achiral Phosphoramidate Mustards as Anticancer Drugs, 51 J. MED. CHEM
2412-2420 (2008) ("Duan").
4 Harry S. Friedman et al., Bevacizumab Alone and in Combination with
Irinotecan in Recurrent Glioblastoma, 27(28) J. CLINICAL ONCOLOGY 4733-
4740 (2009) ("Friedman").
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Appeal 2016-008592
Application 13/809, 135
FINDINGS OF FACT
1. Matteucci discloses: "The present invention provides
compositions and methods for treating cancer and other hyperproliferative
disease conditions with phosphoramidate alkylator prodrugs." Matteucci
2. Matteucci discloses: "The phosphoramidate alkylator prodrug
and their pharmaceutical compositions can be used to treat any type of
cancer in a subject, particularly in a human subject. Cancers that can be
treated include ... glioblastoma multiforma." Id. ,r 297.
3. Matteucci discloses: "In one embodiment, the dose is
administered i. v. daily, either as a monotherapy ( compound of the present
invention alone) or in conjunction ( combination) with standard of care
therapies." Id. ,r 310.
4. Matteucci discloses: "In one version, a phosphoramidate
alkylator prodrug described herein can be used in combination with an
antiangeogenisis inhibitor including but not limited to A vastin and similar
therapeutics." Id. ,r 339. Avastin is bevacizumab. Friedman at 4734.
5. Matteucci discloses:
In one embodiment, a larger dose is administered intermittently
(less frequently); a dose in the range of about 3 to about 20
mg/kg; about 6 to about 10 mg/kg; or 8 mg/kg is administered
on once every three days for two weeks. In another
embodiment, a dose in the range of about 5 to about 30 mg/kg;
about 10 to about 15 mg/kg; or 12.5 mg/kg of the
phosphoramidate alkylator prodrug is administered once a week
for four weeks. In one embodiment, a dose in the range of
about 0.5 to about 8 mg/kg/day is administered for 5 days over
two weekly cycles.
Id. ,I 311.
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Appeal 2016-008592
Application 13/809, 135
6. Matteucci discloses: "In one version of the combination
treatment methods, a subject is treated with an antiangeogenisis inhibitor
and subsequently treated with a phosphoramidate alkylator prodrug." Id. at
,r 339.
7. Matteucci discloses: "In another embodiment, a
phosphoramidate alkylator prodrug is administered after the initiation or
completion of the other cancer therapy." Id. ,r 331.
8. Matteucci discloses:
When a phosphoramidate alkylator prodrug is used in
combination with one or more of the additional therapies, a
phosphoramidate alkylator prodrug and additional therapy can
be administered at the same time or can be administered
separately. For example, if a phosphoramidate alkylator
prodrug is administered with an additional chemotherapeutic
agent, the two agents can be administered simultaneously or
can be administered sequentially with some time between
administrations. One of skill in the art will understand methods
of administering the agents simultaneously and sequentially and
possible time periods between administration.
Id. ,I 336.
9. The Examiner finds, and Appellants do not dispute, that TH-
302 is exemplified in Matteucci's claim 39, which recites "a compound ...
having the formula:"
/ < O:;N ;fr NH
~ :~0 "- I
~e /,p"-._ ~Br
// N
0 H
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Appeal 2016-008592
Application 13/809, 135
Ans. 10; Matteucci claim 39. The Examiner finds, and Appellants do not
dispute, that TH-302 is also exemplified in Matthews' claim 37 and in
Matthews' figures 1, 2, and 3. Ans. 10.
10. Duan discloses: "Hypoxia within the tumor microenvironment
confers resistance to radiation and chemotherapy. The inability to treat the
hypoxic compartment of tumors represents a critical unmet medical need
and an opportunity for the development of novel therapeutics that
selectively target hypoxic tumor cells." Duan at 2412.
11. Duan discloses: "The 2-nitroimidazole containing lead
compound 3b (TH-302) was selectively potent under hypoxia and stable to
liver microsomes." Duan Abstract.
12. Friedman discloses: "Bevacizumab, alone or in combination
with irinotecan, was well tolerated and active in recurrent glioblastoma.
Friedman Abstract.
ANTICIPATION
Appellants argue claims 1 and 5-8 together. We designate claim 1 as
representative.
The Examiner finds that Matteucci anticipates claim 1. We agree with
the Examiner that Matteucci discloses all of the elements of claim 1.
Specifically, Matteucci discloses a method of treating cancer including the
elected glioblastoma. FFl, FF2. The method may comprise combination
therapy using a phosphoramidate alkylator, including the elected hypoxia
activated prodrug TH-302, together with the elected antiangiogenic agent,
bevacizumab. FF3, FF4, FF9. Matteucci also discloses administering the
hypoxia activated prodrug once a week. FF5.
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Application 13/809, 135
Appellants argue that "Matteucci' s teaching is quite general and
suggests nothing about the frequency of dosing of the TH-302 to which it
makes general reference; given the broad scope of the 'phosphoramidate
alkylator prodrug described herein' described in Matteucci, Matteucci does
not anticipate any of the now pending claims." App. Br. 6. We are not
persuaded because Matteucci specifically discloses both the elected prodrug
(FF9) and once weekly dosing of a phosphoramidate alkylator prodrug.
FF5. Accordingly, we affirm the Examiner's rejection of claim 1. Because
they were not argued separately, we also affirm the Examiner's rejection of
claims 5-8.
OBVIOUSNESS OVER MATTEUCCI
Claim 3 depends from claim 1 and additionally requires that "the first
administration of the hypoxia activated prodrug is at least 7 days after the
first administration of the antiangiogenic agent." The Examiner rejected
dependent claim 3 as obvious over Matteucci. Appellants argue that
Matteucci "fails to teach or suggest any particular benefit of administering
the HAP at least 7 days after first administering the antiangiogenic agent."
App. Br. 6. We are not persuaded.
Matteucci teaches once weekly dosing of a phosphoramidate alkylator
prodrug (FF5) and further teaches first administering an antiangiogenesis
inhibitor and subsequently administering a phosphoramidate alkylator
prodrug to treat cancer. FF6 and FF7. In addition, Matteucci teaches that
"[ o ]ne of skill in the art will understand methods of administering the agents
[i.e. the phosphoramidate alkylator prodrug and an additional therapy]
simultaneously and sequentially and possible time periods between
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Application 13/809, 135
administration." FF8. The record thus supports the Examiner's conclusion
that:
at the time of the invention, it would have been prima facie
obvious to one of ordinary skill in the art to optimize the dosing
cycle regimens of hypoxia activated prodrug and antiangiogenic
agent within the parameters suggested by the prior art (i.e. the
hypoxia activated prodrug is administered at least 7 days after
the first administration of the antiangiogenic agent), resulting in
the practice of the method of claim 3 with a reasonable
expectation of success.
Ans. 13. Accordingly, we affirm the Examiner's rejection of claim 3 as
obvious over Matteucci.
OBVIOUSNESS OVER THE COMBINATION OF MATTEUCCI AND
DUAN
Claim 2 depends from claim 1 and additionally requires that "the first
administration of the hypoxia activated prodrug occurs only after
administration of the antiangiogenic agent has resulted in an increased
hypoxic fraction of the cancer." Claim 15 depends from claim 1 and
additionally requires that "the hypoxic fraction of the cancer is measured
prior to or after first administration of the antiangiogenic agent." The
Examiner rejected claims 2 and 15 as obvious over the combination of
Matteucci and Duan. Appellants argue that "[ t ]here is no teaching in Duan
or Matteucci that measurement or status of the hypoxic fraction is an
important consideration when administering combination therapies of a HAP
and an antiangiogenic agent." We are not persuaded because Duan teaches
that hypoxia is an important consideration in cancer treatment (FFlO) and
because Duan further teaches that TH-302 is "selectively potent under
hypoxia." FFl 1. Accordingly, we affirm the Examiner's rejection of claims
2 and 15 as obvious over the combination of Matteucci and Duan.
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Application 13/809, 135
OBVIOUSNESS OVER THE COMBINATION OF MATTEUCCI AND
FRIEDMAN
Appellants argue claims 1 and 5-8 together. We designate claim 1 as
representative.
The Examiner rejected claims 1 and 5-8 as obvious over the
combination of Matteucci and Friedman. Appellants argue that "Friedman
teaches nothing about the benefits of co-administering a HAP and
bevacizumab in the treatment of glioblastoma and so cannot cure the
deficiencies of Matteucci and Duan [sic (Friedman)] with respect to the
instant claims." App. Br. 7. We are not persuaded because Friedman teaches
that bevacizumab is "well tolerated and active in recurrent glioblastoma."
FF12. Moreover, Matteucci also discloses the use ofbevacizumab (FF4),
the use of TH-302 (FF9), and the treatment of glioblastoma. FF2. For these
reasons, we agree with the Examiner that it would have been obvious to the
skilled artisan use the phosphoramidate alkylator prodrug, TH-302, in
combination with the antiangiogenic inhibitor, bevacizumab, for the
treatment glioblastoma. Accordingly, we affirm the Examiner's rejection of
claim 1 as obvious over the combination of Matteucci and Friedman.
Because they were not argued separately we also affirm the Examiner's
rejection of claims 5-8.
SUMMARY
For these reasons and those set forth in the Examiner's Answer and
Final Office Action, we affirm the Examiner's rejection of claims 1 and 5-8
under 35 U.S.C. § 102(b) as anticipated by Matteucci, the Examiner's
rejection of claim 3 under 35 U.S.C. § 103(a) as obvious over Matteucci, the
Examiner's rejection of claims 2 and 15 under 35 U.S.C. § 103(a) as obvious
over the combination of Matteucci and Duan, and the Examiner's rejection
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Application 13/809, 135
of claims 1 and 5-8 under 35 U.S.C. § 103(a) as obvious over the
combination of Matteucci and Friedman.
AFFIRMED
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