Ex Parte Carvalho et al

Patent Trial and Appeal Board

Dec 22, 2016

12881124 (P.T.A.B. Dec. 22, 2016)

United States Patent and Trademark Office
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
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APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
12/881,124 09/13/2010 Leonardo Jose de Moura Carvalho LJBIl 100-1 (999400-3390) 1495
30542 7590 12/27/2016
FOT FY Rr T ARDNFR T T P
EXAMINER
3000 K STREET N.W. PIHONAK, SARAH
SUITE 600
WASHINGTON, DC 20007-5109 ART UNIT PAPER NUMBER
1627
NOTIFICATION DATE DELIVERY MODE
12/27/2016 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte LEONARDO JOSE DE MOURA CARVALHO
and PEDRO CARBALES
Appeal 2014-007175
Application 12/8 81,1241
Technology Center 1600
Before DONALD E. ADAMS, 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
for the treatment of cerebral malaria. The Examiner rejected the claims on
appeal as obvious under 35 U.S.C. § 103(a).
We affirm.
1 According to Appellants, the real party in interest is La Jolla
Bioengineering Institute. App. Br. 2.
Appeal 2014-007175
Application 12/881,124
STATEMENT OF THE CASE
Claims 19-23 are on appeal. Claim 23 is illustrative and reads as
follows:
23. A method for the treatment of cerebral malaria,
said method comprising simultaneously or serially
administering to said mammal a therapeutically effective
amount of an anti-malaria drug, its pharmacologically
acceptable salt, or a hydrate or solvate, and a
therapeutically effective amount of an agent which
promotes vasodilation, its pharmacologically acceptable
salt, or a hydrate or solvate,
wherein said cerebral malaria is characterized in
part by vasoconstriction or vascular collapse caused by
conditions associated with cerebral malaria in a mammal.
The Examiner rejected claims 19-23 under 35 U.S.C. § 103(a) as
unpatentable over the combination of Khaira,2 Childers3, and Bag.4
We affirm.
FINDINGS OF FACT
1. Kharia discloses:
We conclude that falciparum malaria is a cause of DIC
and purpura fulminans. The present case highlights this
rare complication of complicated falciparum malaria and
the need for high index of suspicion of this clinical entity
to differentiate it from other conditions such as collagen
vascular diseases, thrombotic thrombocytopenic purpura,
2 Khaira et al., Rare Presentation of a Common Disease of Tropics, 56
Journal of the Association of Physicians of India, 721-723 (2008)
(“Khaira”).
3 Childers et al., Acute Infectious Purpura Fulminans: A 15-Year
Retrospective Review of 28 Consecutive Cases, The American Surgeon
86-90 (2003) (“Childers”).
4 Bag et al., Complicated Falciparum Malaria, 31 Indian Pediatrics 821—
825 (1994) (“Bag”).
2
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Application 12/881,124
and other conditions associated with peripheral gangrene.
Also, it emphasizes the need to suspect and treat malaria
when a patient presents with fever and purpura especially
after a visit to endemic areas.
Khaira 722.
2. Khaira discloses:
Learning Points:
1. Complicated malaria may mimic meningococcaemia in
its presentation.
2. It should be considered as a differential in cases of
fever with peripheral gangrene.
3. Complicated malaria is a rare cause of DIC the
pathogenesis of which is poorly understood.
4. Prompt management with antimalarials, intravenous
antibiotics and vasodilators is important.
Id.
3. Childers discloses:
Acute infectious purpura fulminans (AIPF) is a rare
syndrome of hemorrhagic infarction of the skin,
extremity loss, and intravascular thrombosis. It
progresses rapidly and is accompanied by disseminated
intravascular coagulation and vascular collapse.
Childers Abstract.
4. Bag discloses:
The most appropriate acceptable definition of severe and
complicated falciparum malaria is recognition of any one
or more of the clinical features such as cerebral malaria,
jaundice, renal failure, pulmonary edema, hypoglycemia,
3
Appeal 2014-007175
Application 12/881,124
circulatory collapse, spontaneous bleeding, repeated
generalized convulsions and acidosis.
Bag at 821.
5. Dondorp5 discloses:
Cerebral malaria is a common presentation of severe
falciparum malaria. It is characterized by coma without
focal signs and complete recovery is remarkable in the
majority of surviving cases. . . . Reduced
microcirculatory flow caused by sequestration of
parasitized erythrocytes and rigid erythrocytes is central
in the pathophysiology of severe disease. A recent trial
has proven that intravenous artesunate should become the
treatment of choice in adults with severe and cerebral
malaria; a similar trial in children is under way.
Supportive treatment tailored to the patient’s specific
organ dysfunctions is essential in this multi-system
disease, ideally in an intensive care unit setting.
Adjunctive treatments have thus far not proven to be
beneficial.
Dondorp 74.
6. Betrosian6 discloses: “Sepsis-induced purpura fulminans is a
rare but life-threatening disorder, characterized by hemorrhagic infarction of
the skin caused by disseminated intravascular coagulation and dermal
vascular thrombosis.” Betrosian Abstract.
5 Dondorp, Pathophysiology, Clinical Presentation and Treatment of
Cerebral Malaria, 10 Neurology Asia 67—77 (2005) (“Dondorp”).
Dondorp was cited by Appellants “to distinguish the treatment modailities
between cerebral malaria and purpura fulminans.” App. Br. 8.
6 Betrosian et al., Purpura Fulminans in Sepsis, 332(6) Am. J. Med. Sci.
339-345 (2006) (“Betrosian”). Betrosian, like Dondorp, was cited by
Appellants “to distinguish the treatment modailities between cerebral
malaria and purpura fulminans.” App. Br. 8.
4
Appeal 2014-007175
Application 12/881,124
7. The Specification states:
An unresolved issue of CM [cerebral malaria]
pathogenesis regards the role of brain hemodynamic
perturbations and ischemia. Direct observation of retinal
microvasculature shows impaired perfusion, vascular
occlusion and ischemia (Beare, et al., JInfect Dis. 2009,
199, 263-271), whereas transcranial Doppler sonography
shows normal or even increased cerebral blood flow
(CBF) velocities in large arteries (Newton, et al., Pediatr
Neural. 1996, 1, 41-49).
Specification 14.
ANALYSIS
Appellants argue claims 19—23 as a group. We designate claim 23 as
representative for claims 19—23.
The Examiner found that Khaira disclosed purpura fulminans, a
potentially fatal disorder caused by disseminated intravascular coagulation
and dermal vascular thrombosis, as occurring from complicated falciparum
malaria. Ans. 3. Khaira discloses treatment of complicated falciparum
malaria by administration of antimalarial drugs and vasodilators. Id.
The Examiner found that Childers disclosed that purpura fulminans
was accompanied by disseminated intravascular coagulation and vascular
collapse. Id. at 4. Based on the teachings of Khaira and Childers, the
Examiner concluded:
[A]s Khaira et[ ] al. teaches the treatment of falciparum
malaria and purpura fulminans associated with
falciparum malaria comprising administration of anti-
malarial drugs and vasodilators, and Childers et[ ] al.
teaches that purpura fulminans is accompanied by
vascular collapse, it would have been obvious that by
treatment of complicated malaria and purpura fulminans
5
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Application 12/881,124
associated with malaria, vascular collapse associated with
the condition would have also been effectively treated.
Id. at 4—5. Neither Khaira nor Childers, however, disclose treatment of
cerebral malaria using a combination of antimalarial drugs and vasodilators.
The Examiner found that Bag disclosed that “complicated falciparum
malaria includes one or more clinical features such as cerebral malaria, renal
failure, circulatory collapse, hypoglycemia, spontaneous bleeding, repeated
convulsions and acidosisa.” Id. at 5. Based on the combined teachings of
Khaira, Childers, and Bag, the Examiner concluded:
[A]s Bag et[] al. teaches that circulatory collapse is a
clinical feature of complicated falciparum malaria, it
would have been obvious that circulatory or vascular
collapse associated with cerebral malaria, which occurred
as a complication of falciparum malaria, would have
been effectively treated by administration of an effective
amount of an anti-malarial drug and a vasodilator.
Id. at 6.
Appellants argue that purpura fulminans and cerebral malaria are
different diseases that are “distinct in both clinical manifestation and
treatment protocol.” App. Br. 10 (relying upon Dondorp and Betrosian as
evidence of the differences between the two diseases). Appellants contend
that “a skilled artisan seeking to treat a patient that is presenting the
symptoms of cerebral malaria would not seek to treat the patient with a
treatment protocol directed to purpura fulminans.” Id. at 6. We are not
persuaded.
Purpura fulminans and cerebral malaria are both complications of
falciparum malaria. See, FF1 and FF4. Both are characterized by vascular
6
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Application 12/881,124
restriction. See, FF3, FF4, FF5 and FF7.7 Khaira teaches treatment of a
malarial patient experiencing the complication of purpura fulminans with
antimalarials and vasodilators. FF2. When combined with Childers, Khaira
teaches the need to treat not just malaria (using an antimalarial drug), but
also vascular complications arising from malaria (using a vasodilator). See,
FF1—3. Accordingly, we agree with the Examiner that it would have been
obvious, in patients experiencing cerebral malaria, to treat the malaria with
an antimalarial drug and to treat any vascular restriction associated with their
cerebral malaria with a vasodilator.8 Appellants’ evidence regarding the
differences between purpura fulminans and cerebral malaria does not
undercut Khaira’s suggestion to treat both the underlying malaria and the
accompanying vascular complication.
Appellants argue that the prior art teaches away from the use of
vasodilators with antimalarials. App. Br. 11. As support, Appellants cite
Spronk’s9 teaching that a patient with “severe DIC and purpura fulminans
developed in a patient with pneumococcal sepsis after the administration of
vasodilators.” Id. at 12. We are not persuaded because Spronk teaches that
the vasodilation therapy was continued and the patient improved. Spronk
7 The claims at issue also posit that the cerebral malaria is “characterized in
part by vasoconstriction or vascular collapse caused by conditions associated
with cerebral malaria in a mammal.”
8 Obviousness is further supported by Dondorp’s teaching in connection
with cerebral malaria that “[sjupportive treatment tailored to the patient's
specific organ dysfunctions is essential in this multi-system disease, ideally
in an intensive care unit setting.” FF6.
9 Spronk et al., Case Report, 95 Thromb. Haemost. 576—578 (2006)
(“Spronk).
7
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Application 12/881,124
576—77. Spronk also reports the successful treatment of another patient with
vasodilators. Id. at 577.
Appellants also cite Leclerc10 as evidence teaching away from the
combination of an antimalarial and a vasodilator. App. Br. 12. Leclerc
states that “treatment of cutaneous necrosis and distal ischemia is difficult
and still controversial: antithrombin, protein C, tissue plasminogen activator
and vasodilator infusion have no proven efficacy.” Leclerc Abstract. While
Leclerc does discourage the use of vasodilators we are not persuaded that it
teaches away from the claimed combination, particularly as Leclerc predates
Khaira’s teachings by seven years.
Accordingly, we affirm the Examiner’s decision to reject claim 23 as
obvious over the combination of Khaira, Childers, and Bag. Because they
were not argued separately claims 19—22 fall with claim 23.
SUMMARY
For these reasons and those set forth in the Examiner's Answer, the
Examiner’s final decision to reject claims 19—23 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
10 Feclerc et al., Treatment of Meningococcal Purpura Fulminans, 8 Supp. 4
Arch Pediatr 677s-678s (2001) (“Feclerc”).
8