Ex Parte Kubata et al

Patent Trial and Appeal Board

Mar 16, 2018

13999318 (P.T.A.B. Mar. 16, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/999,318 02/04/2014
7590
Nash & Titus, LLC
21402 Unison Road
Middleburg, VA 20117
03/16/2018
FIRST NAMED INVENTOR
Bruno K. Kubata
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.
Army 183B 1213
EXAMINER
DA VIS, DEBORAH A
ART UNIT PAPER NUMBER
1655
MAILDATE DELIVERY MODE
03/16/2018 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 BRUNO K. KUBAT A,
SAMUEL K. MARTIN, and WILBUR K. MILHOUS
Appeal2017-005280
Application 13/999,318
Technology Center 1600
Before JEFFREY N. FREDMAN, TA WEN CHANG, and
DAVID COTTA, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal 1 under 35 U.S.C. § 134 involving claims to a method
of treating kinetoplastid infections. The Examiner rejected the claims as
obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We affirm.
Statement of the Case
Background
"Trypanosoma species pathogenic to human beings and domestic
animals in Africa, cause one of the world's most neglected tropical
1 Appellants identify the real party in interest as the U.S. Government as
represented by the Secretary of the Army (see App. Br. 2).
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infections - African trypanosomiasis" (Spec. 1: 18-20). "Treatment of
infected persons with the few available synthetic trypanocidal agents have
shown significant drawbacks related to high cost, host toxicity, limited oral
bioavailability, and a requirement for hospitalization during the entire course
of treatment" (Spec. 3:20-23). "[T]he Chinese plant Artemesia annua has
been used to treat malaria for centuries" (Spec. 5: 1 ). "Artemisinins have
never before been used to treat human and veterinary trypanosomiasis. Until
now, no experimental study has been carried out to establish the
effectiveness of artemisinin or its derivatives on any Trypanosoma species"
(Spec. 5: 14--17).
The Claims
Claims 1, 5-7, 9, and 13 are on appeal. Claim 1 is representative and
reads as follows:
1. A method of treating kinetoplastid infections comprising:
(a) diagnosing a kinetoplastid infection in a mammal; and
(b) administering to said mammal a pharmaceutical
composition wherein said composition contains a
pharmaceutical dose of C1sH220s with a molecular weight of
282, sufficient to decrease said kinetoplastid infection.
The Issue
The Examiner rejected claims 1, 5-7, 9, and 13 under 35 U.S.C.
§ 103(a) as obvious over Yang2 and PubChem3 (Final Act. 2--4).
2 Yang et al., Effects of qinghaosu (artemisinin) and its derivatives on
experimental cutaneous leishmaniasis, 106 PARASITOLOGY 7-11 (1993).
3 PubChem, Artemisinin, http://pubchem.ncbi.nlm.nih.gov/compound/
artemisinin 1-19 (CID 68827, accessed Nov. 14, 2015).
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The Examiner finds Yang "teaches artemisinin is capable of inducing
the killing of intracellular parasitic amastigotes in murine macrophages"
(Final Act. 2). The Examiner finds Yang teaches "artemisinin can kill the
parasites in cell-free cultures" (id. at 3) and that artemisinin derivatives
treated Leishmania infected mice (id. at 2). The Examiner finds Yang
teaches artemisinin is "a useful therapeutic agent in the treatment of clinical
leishmaniasis, which reads on kinetoplastid infection" (id. at 3).
The Examiner finds it obvious "to diagnose kinetoplastid infection"
and that "one skilled in the art would have reasonably understood that if
artemisinin was effective in killing leishmanial parasites in mice, then such
treatment can be extrapolated to a human" (Final Act. 3--4).
The issue with respect to this rejection is: Does the evidence of
record support the Examiner's conclusion that Yang and PubChem render
obvious the diagnosis and treatment of kinetoplastid infections in mammals
with artemisinin as required by claim 1?
Findings of Fact
1. Yang teaches that "artemisinin is the principal component in the
anti-malarial effect of the traditional Chinese herb Artemisia annua" and
"may have broad anti-parasitic potential" (Yang 7, col. 1 ).
2. Yang teaches "L. major promastigotes were cultured for 48 h in
vitro in the presence of graded doses of artemisinin or in medium containing
the diluent Me2SO. The viability of the parasites decreased progressively
with increasing concentrations of artemisinin and no viable parasites were
detectable at around 10-5 M" (Yang 8, col. 2).
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3. Yang teaches "[ m ]urine peritoneal macrophages were infected
with L. major promastigotes for 24 h and then cultured for 48 h with various
concentrations of artemisinin or artemether and the viable amastigotes
estimated. Both artemisinin and artemether are capable of inducing the
killing of the intracellular parasites" but "[ u ]ninfected macrophages cultured
with the highest concentrations of the compounds used (1·23 x 10-4 M) for
the same period remained viable" (Yang 9, col. 1-2).
4. Yang teaches "[ m ]ice infected in the footpad and injected
intramuscularly in the thigh with artemether in oil developed significantly
smaller lesions compared to controls injected with oil alone" (Yang 8, col.
2).
5. Yang teaches "[ m ]ice receiving orally 200 mg/kg/ day of
artemether developed significantly smaller lesions compared to those
receiving oil alone or the untreated controls ... Mice receiving either 200 or
50 mg/kg/day of artemether had significantly lower parasite loads compared
to the controls" (Yang 9, col. 1 ).
6. Yang teaches that "[a ]rtemisinin and its derivatives ... have a
leishmanicidal effect in vitro and, importantly, in vivo. These compounds
appear to exert their effect directly on the leishmanial parasite, since they
can kill the parasites in cell-free cultures" (Yang 9, col. 1-2).
7. Yang teaches "this series of compounds could be potentially
useful therapeutic agents in the treatment of clinical leishmaniasis" (Yang 9,
col. 2).
8. PubChem teaches the molecular formula of artemisinin is
C1sH220s and the molecular weight is 282 (PubChem 1 ).
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9. Original claim 7 teaches the "kinetoplastid infections are
selected from Leishmania infection and trypanosome infection" (Spec.
25:21-22).
Principles of Law
When there is a design need or market pressure to solve a
problem and there are a finite number of identified, predictable
solutions, a person of ordinary skill has good reason to pursue
the known options within his or her technical grasp. If this
leads to the anticipated success, it is likely the product not of
innovation but of ordinary skill and common sense. In that
instance the fact that a combination was obvious to try might
show that it was obvious under
§ 103.
KSR Int 'l Co. v. Teleflex Inc., 550 U.S. 398, 421 (2007).
Analysis
We adopt the Examiner's findings of fact and reasoning regarding the
scope and content of the prior art (Final Act. 2--4; FF 1-9) and agree that the
claims are obvious over Yang and PubChem. We address Appellants'
arguments below.
Appellants contend
Not all artemisinins show antiplasmodial or anti-tumoricidal
activity. The artemisinins in Yang et al. are chemically
different than those of the present invention due to their mode
of extraction. Artemether has a chemical formula of C16H260s
and a MW of 298. Artesunate has a chemical formula of C19H
2sOs and a MW of 384. Therefore, it cannot be said that the
artemisinin C1sH220 with a MW of 282 is obvious from Yang et
al. for in vivo treatment of lieshmaniasis. Yang, et al. did not
take the extra step to test artemisinin in vivo in mammals.
(App. Br. 4).
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We find this argument unpersuasive because Yang expressly teaches
that artemisinin - which PubChem discloses has the formula C15H220 and
MW of 282 (FF 8)- has anti-parasitic potential (FF 1 ), kills Leishmania
major organisms in vitro (FF 2) and in cell culture without killing
macrophages (FF 3). Yang teaches that a derivative of artemisinin,
artemether, kills Leishmania major organisms in mouse footpads by
intramuscular or oral routes (FF 4--5). Yang concludes that artemisinin and
its derivatives treat Leishmania major organisms and may be "useful
therapeutic agents in the treatment of clinical leishmaniasis" (FF 6-7).
Based on these teachings of Yang, we agree with the Examiner that
the ordinary artisan would have found it obvious to try artemisinin as a
therapeutic for clinical leishmaniasis with a reasonable expectation of
success, given that the artemisinin kills Leishmania major organisms
without killing host cells (FF 2-3). Our reviewing court found that in vitro
testing of compounds as therapeutic agents was sufficient to demonstrate the
usefulness of the compounds for an in vivo human setting. See In re Brana,
51F.3d1560, 1566 (Fed. Cir. 1995). Here, where Yang provides direct
evidence of in vitro functionality for artemisinin in treatment of
leishmaniasis and directly suggests clinical treatment where artemisinin is
one of three tested compounds, the person of ordinary skill has good reason
to pursue this known option for leishmaniasis treatment that is within their
technical grasp. See KSR, 550 U.S. at 421.
Appellants contend: "One of ordinary skill in the art would have
known that not all extracts from Artemisia annua result in useful treatments.
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See figures 2 and 3 of the present specification where many derivatives are
provided but only a few showed anti-lieshmaniasis ability" (App. Br. 4).
We find this argument unpersuasive because Yang specifically shows
that artemisinin shows anti-lieshmaniasis ability in vitro (FF 2) without
killing host cells (FF 3), directly demonstrating a reasonable expectation of
success. "'Obviousness does not require absolute predictability of success
... all that is required is a reasonable expectation of success." In re Kubin,
561F.3d1351, 1360 (Fed. Cir. 2009) (citation and alterations omitted).
Appellants contend "the Examiner has not pointed to any evidence of
the Appellant's pharmaceutical composition and method was even tested by
Yang, et al. To the contrary, Yang, et al. is directed to the treatment of
leishmaniasis with the qinghaosu (artemisin) derivatives of artemether and
artesunate" (Reply Br. 2).
We find this argument unpersuasive because Yang expressly teaches
treatment in vitro of L. major promastigotes with artemisinin (FF 2) as well
as the artemether derivative (FF 3 ). Yang's use of the phrase "various
concentrations of artemisinin or artemether" demonstrates that both
compounds were tested in cell culture (FF 3). While we agree with
Appellants that Yang did not exemplify testing in mouse footpads with
artemisinin itself, only testing with the artemether derivative (FF 4--5), we
agree with the Examiner's finding that it would have been obvious to use
artemisinin itself as the therapeutic agent because artemisinin kills L. major
promastigotes in vitro and in cell culture (FF 2-3) and Yang generally
suggests "this series of compounds could be potentially useful therapeutic
agents in the treatment of clinical leishmaniasis" (FF 7). These teachings
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reasonably render it obvious to try artemisinin in the treatment of clinical
leishmaniasis and the in vitro data provides a reasonable expectation of
success for such clinical treatment.
Conclusion of Law
The evidence of record supports the Examiner's conclusion that Yang
and PubChem render obvious the diagnosis and treatment of kinetoplastid
infections in mammals with artemisinin as required by claim 1.
SUMMARY
In summary, we affirm the rejection of claim 1 under
35 U.S.C. § 103(a) as obvious over Yang and PubChem. Claims 5-7, 9, and
13 fall with claim 1.
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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