Ex Parte El Bakkouri et al

Board of Patent Appeals and Interferences

Jan 14, 2010

10882993 (B.P.A.I. Jan. 14, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte KARIM EL BAKKOURI, PATRICK ENGLEBIENNE,
KENNY LEO DE MEIRLEIR, and CHARLES VINCENT HERST
__________

Appeal 2009-012373
Application 10/882,993
Technology Center 1600
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Decided: January 15, 2010
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Before LORA M. GREEN, FRANCISCO C. PRATS, and
MELANIE L. McCOLLUM, Administrative Patent Judges.

GREEN, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. § 134 from the
Examiner’s final rejection of claims 1, 2, 5-10, and 16. We have jurisdiction
under 35 U.S.C. § 6(b).

Appeal 2009-012373
Application 10/882,993

STATEMENT OF THE CASE
The claims are directed to a method of treating a chronic immune
disease, such as chronic fatigue syndrome (“CFS”) or multiple sclerosis
(“MS”) using a β-lactam containing compound. Claims 1 and 2 are
representative of the claims on appeal, and read as follows:
1. A method for treating a host suffering from a chronic immune disease,
said method comprising:
(a) administering to said host an effective amount of a β-lactam
containing compound to treat said host for said chronic immune disease.

2. The method according to Claim 1, wherein said chronic immune
disease is selected from the group consisting of CFS and MS.

The Examiner relies on the following evidence:
Campine et al. US 6,080,554 June 27, 2000
Aranyi et al. US 2003/0114449 A1 June 19, 2003
Suhadolnik WO 98/15646 Apr. 16, 1998
Shapiro WO 00/51623 Sept. 8, 2000
Koppel WO 01/12184 A1 Feb. 22, 2001

Dallegri et al., Cefoperazone Prevents the Inactivation of α1-Antitrypsin by
Activated Neutrophils, 43 ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
2307-2310 (1999).

The following grounds of rejection are before us for review:
I. Claims 1, 2, 5-10, and 16 stand rejected under 35 U.S.C. § 103(a) as
being obvious over the combination of Koppel and Suhadolnik.
II. Claims 1, 2, and 5-9 stand rejected under 35 U.S.C. § 103(a) as being
obvious over the combination of Shapiro or Aranyi as combined with
Dallegri.
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III. Claim 10 stands rejected under 35 U.S.C. § 103(a) as being obvious
over the combination of Shapiro or Aranyi and Dallegri as further combined
with Campine.

We reverse all of the above rejections.

PRINCIPLES OF LAW
The question of obviousness is resolved on the basis of underlying
factual determinations including: (1) the scope and content of the prior art;
(2) the level of ordinary skill in the art; (3) the differences between the
claimed invention and the prior art; and (4) secondary considerations of
nonobviousness, if any. Graham v. John Deere Co., 383 U.S. 1, 17 (1966).
While the analysis under 35 U.S.C. § 103 allows flexibility in
determining whether a claimed invention would have been obvious, KSR
Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007), it still requires showing
that “there was an apparent reason to combine the known elements in the
fashion claimed by the patent at issue.” Id. An invention “composed of
several elements is not proved obvious merely by demonstrating that each of
its elements was, independently, known in the prior art.” Id. “Often, it will
be necessary . . . to look to interrelated teachings of multiple [references] . . .
and the background knowledge possessed by a person having ordinary skill
in the art, all in order to determine whether there was an apparent reason to
combine the known elements in the fashion claimed[.]” Id. “[T]his analysis
should be made explicit,” and it “can be important to identify a reason that
would have prompted a person of ordinary skill in the relevant field to
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combine the elements in the way the claimed new invention does.” Id. “We
must still be careful not to allow hindsight reconstruction of references to
reach the claimed invention without any explanation as to how or why the
references would be combined to produce the claimed invention.”
Innogenetics, N.V. v. Abbott Labs., 512 F.3d 1363, 1374 n.3 (Fed. Cir.
2008).

ISSUE (Rejection I)
The Examiner concludes that claims 1, 2, 5-10, and 16 are rendered
obvious under 35 U.S.C. § 103(a) by the combination of Koppel and
Suhadolnik.
Appellants assert that the Examiner has not provided a valid apparent
reason to combine the teachings of Koppel and Suhadolnik.
Thus, the issue on appeal is: Have Appellants demonstrated that the
Examiner erred in combining the teachings of Koppel and Suhadolnik to
arrive at the claimed method of treating a chronic immune disorder, such as
CFS?

FINDINGS OF FACT
FF1 The Examiner rejects claims 1, 2, 5-10, and 16 under 35 U.S.C.
§ 103(a) as being obvious over the combination of Koppel and Suhadolnik
(Ans. 3).
FF2 The Examiner finds that Koppel teaches the use of a beta-lactam
compound, such as cefoperazone, for the treatment of neural disorders (id. at
4).
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FF3 The Examiner finds further that Koppel teaches that the method is
useful for the treatment of chronic fatigue (id.).
FF4 Koppel is drawn to “pharmaceutical formulations and methods for
treatment of a variety of neurological disease states, including cognitive and
behavioral disorders.” (Koppel 1.)
FF5 Koppel teaches that the invention is based on part that the β-lactam
containing compounds are potent inhibitors of certain mammalian neuro-
peptidases, such as N-acetylated-α-linked acidic peptidases
(NAALADAases) (id.).
FF6 Koppel teaches that neurological disease states that may be treated
include, among other things, chronic fatigue (id. at 16; see also id. at 15-22).
FF7 The Examiner notes that “Koppel does not teach expressly the
employment of beta-lactam for treatment of chronic fatigue syndrome.”
(Ans. 4.)
FF8 The Examiner relies on Suhadolnik for teaching that “one of the major
symptoms of chronic fatigue syndrome is chronic fatigue,” and that the
syndrome may be diagnosed by measuring the amount of RNase L
fragments (id.).
FF9 Suhadolnik teaches that CFS “is an illness of unknown etiology, often
associated with sudden onset, flu-like symptoms, debilitating fatigue, low-
grade fever, myalgia and neurocognitive dysfunction,” and that “[d]iagnosis
of CFS remains one of exclusion.” (Suhadolnik 1.)
FF10 Suhadolnik teaches further that “[a]n accumulating body of evidence
suggests that CFS is associated with disregulation of both humoral and
cellular immunity, including mitogen response, reactivation of viruses,
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abnormal cytokine production, diminished natural killer cell function and
changes in intermediary metabolites.” (Id. at 2.)
FF11 The Examiner concludes that it would have been obvious to the
ordinary artisan at the time of invention “to treat chronic fatigue syndrome
with Koppel’s method as chronic fatigue is one of the major symptoms of
chronic fatigue syndrome (CFS).” (Ans. 4.)
FF12 The Examiner notes further:
It is well-settled fact that in treating syndromes, therapy is
directed to alleviating symptomology. Similarly, faced with a
disease state, the skilled artisan would have been motivated to
treat these symptoms with medicaments old and well known to
treat the disease state; regardless the underlying etiology. Thus
regardless the etiology, to treat chronic fatigue with old and
well-known cephem would have been obvious to the normal
skilled artisan.

(Id. at 6.)

ANALYSIS
Appellants argue that “there is no valid apparent reason to combine
the teachings of Koppel and Suhadolnik as asserted by the Office because
one cannot reasonably link the common condition of chronic fatigue from
Koppel with the symptom of CFS from Suhadolnik.” (App. Br. 6-7.)
Koppel, Appellants assert, teaches that chronic fatigue is a
neurological disease state (id. at 7-8.) Moreover, Appellants argue, chronic
fatigue is a “prolonged feeling of tiredness,” and is “a symptom of many
illnesses.” (Id. at 8.) Suhadolnik, Appellants argue, teaches that
“‘debilitating fatigue’” is one of the symptoms of CFS, and also teaches
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“diagnosing CFS through detection of a unique molecular marker, RNase L
fragments, in certain cells.” (Id. at 9.)
Appellants assert that the ordinary artisan would not link the “‘chronic
fatigue’” of Koppel with the “‘debilitating fatigue’” of Suhadolnik, as the
“fatigue that characterizes CFS is particular.” (Id.) Appellants cite the
official definition of CFS as set forth by the US Centers for Disease Control,
which specifies that “the fatigue must last for at least six months, must not
be alleviated by rest, and must be exacerbated by physical exercise.” (Id.)
Koppel, Appellants assert, does not teach its “‘chronic fatigue’” includes
those symptoms. (Id.) Appellants further cite the Myalgic
Encephalomyelitis Society of America for its teaching that “chronic fatigue”
should not be confused with CFS, and that CFS is “distinct, biological,
clinical disorder.” (Id.) Thus, Appellants assert, “one of ordinary skill in the
art would find no indication that CFS is treatable by β-lactam other than the
mere disclosure of neurological ‘chronic fatigue’ treatable by β-lactam.”
(Id. at 11.)
We agree with Appellants’ reasoning that the Examiner has failed to
establish a prima facie case of obviousness. Suhadolnik teaches that CFS is
an illness of unknown etiology, but that evidence is mounting that it is
associated with disregulation of both humoral and cellular immunity.
Koppel, on the other hand, teaches the use of β-lactam compounds to treat a
variety of neurological disease states, including cognitive and behavioral
disorders. Koppel then lists “chronic fatigue” among a long list of
neurological disorders in which NAALADase inhibitors may be used.
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The Examiner has not provided a reason as to why the ordinary artisan
would use a NAALADase inhibitor, which Koppel teaches may be used to
treat a variety of neurological disease states, to treat CFS, an illness of
unknown etiology, but which appears to be an immunological disorder.
As to the Examiner’s argument that therapy is directed to alleviating
symptomology, claim 1 is drawn to a “method for treating a host suffering
from a chronic immune disease” comprising administering “an effective
amount of a β-lactam containing compound to treat said host for said chronic
immune disease.” Thus, the claim requires treatment of a chronic immune
disease, and not a symptom of such a disease, for example the symptom of
chronic fatigue in CFS. See Rapoport v. Dement, 254 F.3d 1053, 1059-60
(Fed. Cir. 2001) (noting that “‘treatment of sleep apnea[]’” was properly
interpreted as limited to the underlying apnea itself; claim term did not
include treatment of anxiety that can occur secondary to sleep apnea).

CONCLUSION(S) OF LAW
We conclude that Appellants have demonstrated that the Examiner
erred in combining the teachings of Koppel and Suhadolnik to arrive at the
claimed method of treating a chronic immune disorder, such as CFS.
We thus reverse the rejection of claims 1, 2, 5-10, and 16 under 35
U.S.C. § 103(a) as being obvious over the combination of Koppel and
Suhadolnik.

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ISSUE
The Examiner concludes that claims 1, 2, and 5-9 are rendered
obvious by the combination of Shapiro or Aranyi as combined with Dallegri,
and that claim 10 is rendered obvious by the combination of Shapiro or
Aranyi and Dallegri as further combined with Campine.
Appellants assert that Dallegri does not teach or suggest that β-lactam
inhibit elastase.
Thus, the issue on appeal is: Have Appellants demonstrated that the
Examiner erred in finding that Dallegri teaches or suggest that β-lactam
inhibit elastase, and thus erred in concluding that the combination of Shapiro
or Aranyi as combined with Dallegri renders the claimed method of treating
a chronic immune disease, such as MS, obvious?

FINDINGS OF FACT
FF13 The Examiner rejects claims 1, 2, and 5-9 under 35 U.S.C. § 103(a) as
being obvious over the combination of Shapiro or Aranyi as combined with
Dallegri (Ans. 4).
FF14 The Examiner finds that Shapiro teaches “a method of treating
multiple sclerosis comprising administering to the subject an elastase
inhibitor.” (Id.)
FF15 The Examiner finds that Aranyi teaches “a method of treating multiple
sclerosis comprising administering to the subject an elastase inhibitor.” (Id.
at 5.)
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FF16 The Examiner notes that neither Shapiro nor Aranyi expressly teaches
“the employment of beta-lactam as the elastase inhibitor for treating multiple
sclerosis.” (Id.)
FF17 The Examiner cites Dallegri for teaching that “[ce]foperazone
prevents the inactivation of alpha1 antitrypsin and thereby inhibits the
activity of elastase.” (Id.) Thus, according to the Examiner, Dallegri
“discloses that the beta-lactam herein is old and well-known protease
inhibitor.” (Id. at 7.)
FF18 Dallegri teaches that cefoperazone prevents “α1-antitrypsin
inactivation by neotrophils” as well as “reduce[s] the free elastase activity in
a neutrophil suspension supplemented with α1-antitrypsin without affecting
the cells’ ability to release elastase.” (Dallegri, Abstract.)
FF19 Dallegri teaches that cefoperazone “is able to trap HOCl that is
generated by neutrophils,” and that “HOCl or other neutrophil-derived
oxidants directly inactivate neutrophil elastase by a cefoperazone-inhibitable
process.” (Id. at 2307, second column.)
FF20 Thus, Dallegri does not teach that cefoperazone is an elastase
inhibitor, but that cefoperazone “inactivates hypochlorous acid before its
reaction with α1-antitrypsin, thereby permitting the anti-protease-mediated
blockade of released elastase.” (Id. at Abstract.)
FF21 The Examiner concludes that it would have been obvious at the time
of invention to use cefoperazone as the elastase inhibitor in the treatment of
MS “because cefoperazone is known to be useful as elastase inhibitor.”
(Ans. 5.)
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FF22 The Examiner also rejects claim 10 under 35 U.S.C. § 103(a) as being
obvious over the combination of Shapiro or Aranyi and Dallegri as further
combined with Campine (id.).
FF23 The Examiner relies on Campine for teaching a diagnostic method for
MS (id.).

ANALYSIS
Appellants argue that Dallegri “teaches that cefoperazone, a β-lactam
compound, prevents inactivation of α1-AT by stimulated neutrophils, thereby
maintaining α1-AT-mediated blockade of released elastase.” (App. Br. 14-
15.) Dallegri, Appellants assert, nowhere indicates “that β-lactams inhibit
elastase,” and thus “does not teach or suggest that a β-lactam compound
inhibits an elastase.” (Id. at 15.)
Appellants argue further that while Dallegri teaches that cefoperazone
has an antiprotease effect, that is “not the same as a compound that inhibits a
protease.” (Id.) Further, Appellants assert, the “Examiner does not provide
any reasoning as to why the use of a compound with an anti-elastase effect
in a certain condition would make up the alleged deficiency of the
employment of an elastase inhibitor in MS patients.” (Id.) Appellants thus
argue that as “the combination of Sharpiro [sic, Shapiro] or Aranyi’s method
of administering an elastase inhibitor (e.g., α1-AT) for treatment of MS and
Dallegri’s disclosure β-lactam that keeps α1-AT active does not teach or
suggest the use of a β-lactam compound to treat MS.” (Id.)
We agree with Appellants reasoning. Specifically, the Examiner has
provided no reasoning as to why one would use cefoperazone, which
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Dallegri teaches inactivates hypochlorous acid before its reaction with α1-
antitrypsin, thereby permitting the anti-protease-mediated blockade of
released elastase, for the elastase inhibitor of Shapiro or Aranyi.

CONCLUSIONS OF LAW
We conclude that Appellants have demonstrated that the Examiner
erred in finding that Dallegri teaches or suggest that β-lactam inhibit
elastase, and thus erred in concluding that the combination of Shapiro or
Aranyi as combined with Dallegri renders the claimed method of treating a
chronic immune disease, such as MS, obvious.
We thus reverse the rejection of claims 1, 2, and 5-9 under 35 U.S.C.
§ 103(a) as being obvious over the combination of Shapiro or Aranyi as
combined with Dallegri.
As to the rejection of claim 10 under 35 U.S.C. § 103(a) as being
obvious over the combination of Shapiro or Aranyi and Dallegri as further
combined with Campine, as Campine does not remedy the deficiencies of
the combination of Shapiro or Aranyi and Dallegri, we are compelled to
reverse this rejection as well.

REVERSED

cdc

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