Ex Parte Theobald et al

Board of Patent Appeals and Interferences

Jan 13, 2012

11421615 (B.P.A.I. Jan. 13, 2012)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte KLAUS THEOBALD and JERROLD H. LEVY
__________

Appeal 2011-011509
Application 11/421,615
Technology Center 1600
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Before FRANCISCO C. PRATS, MELANIE L. McCOLLUM, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
for inhibiting undesirable thrombin generation using doxycycline. The
Examiner rejected the claims as obvious. We have jurisdiction under 35
U.S.C. § 6(b). We reverse.

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Statement of the Case
Background
“In order to prevent or treat conditions and disorders associated with
abnormal coagulation, therapeutic methods to inhibit clot formation or to
dissolve clots have been developed” (Spec. 2, ll. 4-6). The Specification
teaches “a method for inhibiting undesirable thrombin generation. The
method comprises administering an effective amount of a non-antibacterial
tetracycline formulation” (Spec. 4, ll. 20-22).
The Claims
Claims 1, 16-18, 33 and 34 are on appeal. Claim 1 is representative
and reads as follows:
1. A method for inhibiting undesirable thrombin
generation in a mammal in need thereof, the method
comprising administering to the mammal an effective
amount of a non-antibacterial tetracycline formulation
wherein the non-antibacterial tetracycline formulation
comprises an antibacterial tetracycline in a sub-antibacterial
amount, and the antibacterial tetracycline is doxycycline.

The Issue

The Examiner rejected claims 1, 16-18, 33, and 34 under 35 U.S.C. §
103(a) as obvious over Levy1 (Ans. 4-6).
The Examiner finds that Levy teaches “a method of treating ischemia
or stroke in a subject by administering an effective amount of a tetracycline
compound” (Ans. 5). The Examiner finds that “[d]osages of the active
agents range from 0.0001 to 100 mg per kilogram of body weight per day”

1 Levy et al., US 2004/0063674 A1, published Apr. 1, 2004.
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(Ans. 5). The Examiner finds that Levy teaches “a tetracycline of formula I
in claim 42. It is noted that this formula encompasses doxycycline, where
R2, R2', R3, R4', R4", R6, R6', R7, R8, R9, R10, R11, R12 are hydrogen, R4
is NR4'R4", R5 is hydroxyl, and X is CR6'R6” (Ans. 5).
Appellants contend that by “the starkest of contrasts, Levy et al.
expressly disclaims doxycycline from the definition of the term ‘tetracycline
compound.’ Thus, in paragraph [0045], Levy et al. explicitly and
unambiguously states that ‘[t]he term ‘tetracycline compound’ does not
include ... doxycycline ....’” (App. Br. 5). Appellants contend that “in his
interpretation of Levy et al., the examiner placed excessive emphasis on the
published claims, while disregarding the ‘dispositive’ disclaimer in Levy et
al. By doing so, the examiner failed to appreciate that doxycycline ‘is
deemed to be outside the reach of the claims of the (Levy et al.) patent’”
(App. Br. 7).
Appellants contend that “a person having ordinary skill in the art
would not have had a reasonable expectation that 2-alkyl doxycycline and
doxycycline have the same antibiotic activity” (App. Br. 9). Appellants
contend that “[t]herefore, a person having ordinary skill would also not have
a reasonable expectation that 2-alkyl doxycycline and doxycycline have the
same thrombin inhibition activity” (App. Br. 9).
Appellants contend that “nothing in Levy et al., in the background
section of the present specification, or in a combination of Levy et al. and the
background section would reasonably suggest to a person having ordinary
skill in the art that a tetracycline compound might inhibit undesirable
thrombin generation” (App. Br. 10).
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The issue with respect to this rejection is: Does the evidence of record
support the Examiner’s conclusion that Levy renders the use of doxycycline
in the method of claim 1 obvious?
Findings of Fact
1. Levy teaches a “method for treating ischemia or stroke in a
subject. The method includes administering to a subject an effective amount
of a tetracycline compound” (Levy 2 ¶ 0034).
2. Levy teaches that the “term ‘tetracycline compound’ does not
include minocycline, doxycycline, or tetracycline. The term includes
substituted tetracycline compounds or compounds with a similar ring
structure to tetracycline” (Levy 3 ¶ 0045).
3. Levy teaches that “intravenous and subcutaneous doses of the
compounds of this invention for a patient will range from about 0.0001 to
about 100 mg per kilogram of body weight per day” (Levy 279 ¶ 0238).
4. Levy teaches a treatment method using the compound of claim
42, where the core structure is reproduced below:

The Examiner finds that this tetracycline formula encompasses doxycycline
(Levy 361, claim 42; Ans. 5).

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5. Levy teaches the use of 2-alkyl doxycycline as reproduced
below:

“In other embodiments, compounds of the invention include tetracycline
compounds wherein R2 is alkyl (e.g., 2-alkyl doxycycline compounds)”
(Levy 13 ¶ 0151).
6. The Specification teaches that:
Abnormalities in the coagulation cascade have been
implicated in numerous vascular diseases and conditions.
Such diseases and conditions include cardiovascular
diseases (e.g., thrombosis such as deep vein thrombosis,
myocardial thrombosis, etc., and peripheral arterial
occlusion, coronary artery disease, myocardial ischemia,
pulmonary embolism, etc.), cerebrovascular diseases (e.g.
stroke such as ischemic stroke and thrombotic stroke

(Spec 1, l. 21 to 2, l. 2).
Principles of Law
“In proceedings before the Patent and Trademark Office, the
Examiner bears the burden of establishing a prima facie case of obviousness
based upon the prior art.” In re Fritch, 972 F.2d 1260, 1265 (Fed. Cir. 1992).
“[R]ejections on obviousness grounds cannot be sustained by mere
conclusory statements; instead, there must be some articulated reasoning
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with some rational underpinning to support the legal conclusion of
obviousness.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007).
Analysis
The Examiner relies upon Levy to suggest the administration of
doxycycline for treatment of undesirable thrombin generation (Ans. 5). The
Examiner also relies upon claim 42 of Levy to show that Levy encompasses
the use of doxycycline (Ans. 5). The Examiner concedes that Levy does not
specifically disclose “a method of inhibiting undesirable thrombin
generation in a human” (Ans. 5). The Examiner relies upon the correlation
of treatment of stroke and inhibiting undesirable thrombin generation found
in the Specification to connect the treatment of Levy with the treatment
required by the instant claims.
Appellants contend that by “the starkest of contrasts, Levy et al.
expressly disclaims doxycycline from the definition of the term ‘tetracycline
compound.’ Thus, in paragraph [0045], Levy et al. explicitly and
unambiguously states that ‘[t]he term ‘tetracycline compound’ does not
include ... doxycycline ....’” (App. Br. 5).
We agree with Appellants that Levy does not suggest the use of
doxycycline as a treatment (see FF 2). We also agree that the disclaimer in
paragraph [0045] of Levy operates to exclude doxycycline from claim 42,
since the preamble of Levy’s claim 42 states “said tetracycline compound is
of formula I” and paragraph [0045] defines “tetracycline compound” to
exclude doxycycline. See Serrano v. Telular Corp., 111 F.3d 1578, 1582
(Fed. Cir. 1997) (“The inventors’ definition and explanation of the meaning
of the word … as evidenced by the specification, controls the interpretation
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of that claim term). Here, the phrase “tetracycline compound” is expressly
defined to exclude doxycycline, so the use of that term in claim 42 is
controlled by the express definition in Levy’s specification.
We therefore disagree with the Examiner’s position “that doxycycline
is within the scope of the invention taught by Levy” (Ans. 7). We conclude
that doxycycline is not within the scope of Levy’s invention, as expressly
stated by Levy (FF 2).
The Examiner finds “that doxycycline is obvious over the teaching of
2-alkyl doxycycline by Levy” (Ans. 9).
We are not persuaded. We agree with Appellants that “a person
having ordinary skill would . . . not have a reasonable expectation that 2-
alkyl doxycycline and doxycycline have the same thrombin inhibition
activity” (App. Br. 9). The issue is that the Examiner has not established, by
evidence, an equivalence between 2-alkyl doxycycline and doxycycline for
purposes of treating undesirable thrombin generation.
While Levy’s disclaimer of doxycycline is not a teaching away, since
Levy does not disparage the use of doxycycline, the Examiner has provided
no positive, evidence based reason to use doxycycline in a method for
inhibiting undesirable thrombin generation. It is the burden of the Examiner
to establish equivalence between 2-alkyl doxycycline and doxycycline in
order to support an obviousness rejection, and there is no evidence of record
that these compounds would be equivalent in function for the purpose
claimed. The fact that Levy disclaimed the use of doxycycline supports a
conclusion of non-equivalence, not one of equivalence (FF 2).
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Conclusion of Law
The evidence of record does not support the Examiner’s conclusion
that Levy renders the use of doxycycline in the method of claim 1 obvious.

SUMMARY
In summary, we reverse the rejection of claims 1, 16-18, 33, and 34
under 35 U.S.C. § 103(a) as obvious over Levy.

REVERSED

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