Ex Parte Diorio et al

Board of Patent Appeals and Interferences

Sep 14, 2011

11642509 (B.P.A.I. Sep. 14, 2011)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte CHRISTOPHER R. DIORIO, SYED M. SHAH,
and KADUM A. ALI
__________

Appeal 2010-009913
Application 11/642,509
Technology Center 1600
__________

Before ERIC GRIMES, LORA M. GREEN, and JEFFREY N. FREDMAN,
Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to an
enteric-coated antibiotic, which the Examiner has rejected as obvious. We
have jurisdiction under 35 U.S.C. § 6(b). We affirm-in-part.
STATEMENT OF THE CASE
The Specification discloses that tigecycline is a known antibiotic of
the tetracycline family (Spec. 2, ¶¶ 3, 4). “Although an intravenous
formulation of tigecycline has been prepared, simple oral immediate release
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prototypes containing tigecycline have resulted in poor bioavailability in
animals” (id. at 3, ¶ 5). The Specification discloses that enterically coating
tigecycline improves bioavailability after oral administration (see id. at 27,
¶ 80 and 35, ¶ 99).
Claims 1-19 are on appeal. Claim 1 is representative and reads as
follows:
1. A pharmaceutical composition comprising tigecycline having at least
one enteric coating.

The claims stand rejected under 35 U.S.C. § 103(a)
1
as follows:
• Claims 1-4, 7-9, 12, 13, 16, and 19 based on Leach
2
(Answer 5);
• Claims 1, 3-5, 7-14, 16, and 19 based on Levy
3
(Answer 7);
• Claim 18 based on Levy and Remington‟s
4
(Answer 9); and
• Claims 2, 6, 15, and 17 based on Levy, Valerose,
5
and Fleming
6

(Answer 10).

1
The Answer also includes a provisional rejection for obviousness-type
double patenting based on application 11/642,522 (Answer 3). According to
USPTO records, however, the „522 application was abandoned on Nov. 10,
2010, so the provisional rejection is moot.
2
Leach et al., US 2004/0147441 A1, Jul. 29, 2004.
3
Levy et al., US 2004/0063674 A1, Apr. 1, 2004.
4
Alfonso R. Gennaro (ed.), REMINGTON: THE SCIENCE AND PRACTICE OF
PHARMACY 1646 (Mack Publishing Co., Easton, PA) 19
th
ed., 1995.
5
Valerose et al., EP 0 310 814, published Apr. 12, 1989.
6
Fleming, GB 2 406 517 A, published Apr. 6, 2005.
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I.
Issue
The Examiner has rejected claims 1-4, 7-9, 12, 13, 16, and 19 as
obvious in view of Leach. The Examiner finds that Leach discloses “orally
administering a composition[ ] comprising at least one antibiotic such as
tigecycline, to prevent bacteremia by decolonizing the intestinal tract of a
patient” (Answer 5). The Examiner also finds that Leach discloses
“[f]ormulations which target the antibiotic release to the small intestine . . .
by encapsulating the antibiotic composition with an enteric coating” and
therefore it would have been obvious to provide a tigecycline formulation
with an enteric coating “for targeted release to the small intestines” (id. at 6).
Appellants contend that “Leach contemplates the use of many
different antibiotics” (Appeal Br. 4), and because of the differences between
antibiotics “a person skilled in the art would not be able to predict whether a
specific antibiotic could be successfully formulated for a desired purpose”
(id. at 5). Appellants also contend that Leach does not provide examples of
specific formulations with specific antibiotics or “guidance as to formulating
any specific antibiotics” (id.) and therefore “does not provide sufficient
guidance to enable a person skilled in the art to practice any of its disclosed
formulations, let alone provide a reasonable expectation that such
formulations would work” (id.).
The issue with respect to this rejection is: Does Leach provide
sufficient direction to provide a person of ordinary skill in the art a reason to
combine tigecycline and an enteric coating, with a reasonable expectation of
success?
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Findings of Fact
1. Leach discloses that “blood infections in patients whose intestinal
tracts are colonized by either Gram-positive bacteria, Gram-negative
bacteria, or both may be prevented by substantially decolonizing the
intestinal tracts by orally administering an effective amount of one or more
of the compounds . . . provided in Table 1” (Leach 1, ¶ 9).
2. The compounds provided in Leach‟s Table 1 include tigecycline
(id. at 4, ¶ 36).
3. Leach discloses that “[a]ntibiotic-containing formulations suitable
for ingestion include, for example, a pill, capsule, tablet,” etc. (id. at 5, ¶ 50).
4. Leach discloses that “the pharmaceutical formulations may be
designed to provide either immediate or controlled release of the antibiotic
upon reaching the target site” (id.).
5. Leach discloses that “[f]ormulations which target the antibiotic
release to particular regions of the intestinal tract can also be prepared. The
antibiotic can be encapsulated in an enteric coating which prevents . . .
release from occurring in the stomach, but dissolves readily in the mildly
acidic or neutral pH environment of the small intestine.” (Id. at 6, ¶ 54.)
6. The Specification discloses that “coating a tigecycline with at least
one enteric coating . . . can be performed using any known process in the art,
such as by introducing the tigecycline into a fluid bed processor (or other
coating device, such as a pan coater) containing the enteric coating material”
(Spec. 11, ¶ 38).
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Analysis
Leach discloses treating patients by orally administering an antibiotic,
such as tigecycline, to kill bacteria in the intestinal tract. Leach expressly
suggests making formulations that target the small intestine by encapsulating
the antibiotic in an enteric coating. We agree with the Examiner that, based
on these disclosures, a person of ordinary skill in the art would have
considered it obvious to make enteric-coated tigecycline for use in Leach‟s
treatment method.
Appellants argue that Leach discloses that many different antibiotics
can be used in its method and “due to the significant differences between the
antibiotics disclosed in Leach, a person skilled in the art would not be able to
predict whether a specific antibiotic could be successfully formulated for a
desired purpose” (Appeal Br. 5). Appellants argue that Leach does not
provide examples of specific formulations or guidance in formulating any
specific antibiotics (id.) and therefore does not enable practice of any of its
disclosed formulations or provide a reasonable expectation that the
formulations would work (id.).
This argument is not persuasive. The instant Specification itself
provides evidence that methods of providing an enteric coating are known in
the art, so the fact that Leach does not disclose such methods does not make
the reference nonenabling. Appellants have provided no evidence to support
their position that a skilled worker would not have been able to make
enteric-coated tigecycline based on Leach‟s disclosure and the existing
knowledge in the art.
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Appellants also argue that “[n]othing in Leach teaches how to make
[a] tigecycline formulation for treating a GI tract infection having the
bioavailability of the claimed invention” (Appeal Br. 4).
This argument is also unpersuasive. Claim 1 does not require the
claimed composition to have any particular bioavailability, and the
Specification discloses that the claimed composition is made using “any
known process” (FF 6) for providing an enteric coating. Appellants have not
shown that the enteric-coated tigecycline made obvious by Leach differs in
any way from the claimed enteric-coated tigecycline.
Conclusion of Law
Leach provides sufficient direction to provide a person of ordinary
skill in the art a reason to combine tigecycline and an enteric coating, with a
reasonable expectation of success. We therefore affirm the rejection of
claim 1 based on Leach. Claims 2-4, 7-9, 12, 13, 16, and 19 fall with claim
1 because they were not argued separately. 37 C.F.R. § 41.37(c)(1)(vii).
II.
The Examiner has rejected claims 1, 3-5, 7-14, 16, and 19 as obvious
based on Levy (Answer 7). The Examiner has also rejected claim 18 as
obvious based on Levy and Remington‟s (id. at 9) and claims 2, 6, 15, and
17 as obvious based on Levy, Valerose, and Fleming (id. at 10). Because
the same issue is dispositive with respect to each of these rejections, we will
address them together.
The Examiner finds that Levy discloses treating diseases using
tetracycline compounds, including tigecycline, having a target therapeutic
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activity (Answer 7). The Examiner also finds that Levy discloses that its
compositions can be provided as capsules, pills, or tablets (id.) that “may be
coated with an enteric coating” (id. at 8). The Examiner concludes that it
would have been obvious based on Levy‟s teachings to formulate enteric-
coated tigecycline “in order to provide pharmaceutical compositions
comprising tigecycline for targeted release” (id.).
Appellants contend that “a person skilled in the art would not be
motivated to use the teachings of Levy to formulate tigecycline
compositions for bacterial infections” (Answer 6) because the “target
therapeutic activity” relied on by Levy refers to activities that differ from the
tetracycline derivatives‟ antibacterial activity (id.). Appellants also point out
that Levy discloses “numerous pharmaceutical formulations” and “hundreds
of different tetracyline [sic] compounds” (id.).
We agree with Appellants that a person of ordinary skill in the art
would not have been led to make the claimed enteric-coated tigecycline
based on Levy‟s disclosure. Levy is directed to “a method for treating a
disease with a tetracycline compound having a target therapeutic activity”
(Levy 1, ¶ 9). As Appellants point out, Levy defines “targeted therapeutic
activity” to mean “activities of tetracycline compounds in a subject that
differ from antibacterial and/or antiinfective activity” (id. at 3, ¶ 44). Levy
proposes to treat a variety of disorders with its method (see id. at 2, ¶¶ 32-
38) but those disorder do not include bacterial infection.
Levy discloses “pharmaceutical compositions comprising an effective
amount of a substituted tetracycline compound . . . of the invention and a
pharmaceutically acceptable carrier” (id. at 276, ¶ 203). Levy discloses that
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the compositions can be formulated for oral administration as capsules,
tablets, etc. (id. at 277, ¶ 211) and the “tablets, and other solid dosage forms
. . . may optionally be scored or prepared with coatings and shells, such as
enteric coatings and other coatings well known in the pharmaceutical-
formulating art” (id. at 277, ¶ 213).
Levy discloses that “[e]xamples of substituted tetracycline compounds
of the invention include compounds of Tables 2 and 3” (id. at 13, ¶ 152).
Levy‟s Table 2 begins on page 26 and ends on page 268. Levy‟s Table 3
begins on page 285 and ends on page 355; Table 3 includes tigecycline
(page 310, compound DZ).
Thus, to reach the claimed enteric-coated tigecycline based on Levy‟s
teachings, a person of ordinary skill in the art would need to choose
tigecycline from Levy‟s 300-plus pages of different tetracycline derivatives
and choose to formulate it with an enteric coating for use in treating one of
the disorders disclosed by Levy, none of which is specific to the small
intestine.
We do not agree with the Examiner that a skilled worker would have
been led to combine the relevant parts of Levy based on a desire for
“targeted release” (Answer 8), because the Examiner has not provided any
reason for concluding that release in the small intestine would be beneficial
in treating the diseases disclosed by Levy. The Examiner cites nothing in
Remington‟s, Valerose, or Fleming that makes up for the deficiency of
Levy. We are therefore compelled to reverse the rejections based on Levy,
alone or combined with the other references.
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SUMMARY
We affirm the rejection of claims 1-4, 7-9, 12, 13, 16, and 19 based on
Leach. We reverse the rejections based on Levy, alone or combined with
Remington‟s or Valerose and Fleming.
TIME PERIOD FOR RESPONSE
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-IN-PART

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