Ex Parte Burgard et al

Board of Patent Appeals and Interferences

Dec 14, 2007

10296418 (B.P.A.I. Dec. 14, 2007)

UNITED STATES PATENT AND TRADEMARK OFFICE
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BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
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Ex parte GUNTHER BURGARD and HEINZ DIETER CULLMANN
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Appeal 2007-4161
Application 10/296,418
Technology Center 1600
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Decided: December 14, 2007
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Before DEMETRA J. MILLS, ERIC GRIMES, and LORA M. GREEN,
Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
of treating cardiovascular disease. The Examiner has rejected the claims as
obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm.
BACKGROUND
The Specification discloses “the use of hyaluronidase for prevention
and treatment of cardiovascular diseases such as coronary heart disease as
well as other arterioscleroses as well as for prevention of restenosis in
patients who have already been subjected to a coronary intervention.
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Coronary interventions include, for example, stent implantation, balloon
dilatation, rotablation and bypass operations (arterio-occlusive disease
treatments)” (Specification 1).
DISCUSSION
1. CLAIMS
Claims 7-31 are pending and on appeal. Claim 7 is representative and
reads as follows:
Claim 7. A method of treating cardiovascular disease, which method
comprises intravenously administering to a patient at least 6,000 units per
day of hyaluronidase for at least four weeks, whereupon cardiovascular
disease in the patient is treated.

2. OBVIOUSNESS I
Claims 7-9, 13-15, 19-21, 25-27, and 31 stand rejected under 35
U.S.C. § 103 as obvious in view of Cullmann1 and Johnsson.2 Claims 8, 9,
13-15, 19-21, 25-27, and 31 have not been argued separately and therefore
stand or fall with claim 7. 37 C.F.R. § 41.37(c)(1)(vii).
The Examiner relies on Cullmann for disclosing “the treatment of
cardiovascular diseases by the intravenous (i.v.) administration of
hyaluronidase to a patient” (Answer 3). The Examiner finds that Cullmann
discloses administering 1500-4500 units of the enzyme three times per week
(id. at 4).
The Examiner further finds that “Cullmann does not expressly
disclose administering at least 6,000 units per day of hyaluronidase for at

1 Cullmann, DE 19501378 A1, Aug. 8, 1996. Our citations are to the
English translation (of record).
2 Johnsson, WO 99/02181, Jan. 21, 1999
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least four weeks” (id.), as required by claim 7. The Examiner finds that
Johnsson “discloses ‘the use of hyaluronidase for the treatment of conditions
. . . in a mammal’ (abstract) using a daily dosage of from 1 to 80,000 units
per kg body weight, which may be administered systemically” (Answer 5).
The Examiner concludes that, “[a]t the time the invention was made,
it would have been obvious to a person of ordinary skill in the art to have
varied the dosage and length of hyaluronidase administration for the
treatment of cardiovascular disease in a patient, including using the dosages
and lengths of administration recited in the claims” because “the selection of
appropriate dosages and hyaluronidase therapy lengths would have been a
routine matter of optimizing a result-effective parameter” (id. at 4).
We conclude that the Examiner has set forth a prima facie case that
the claims would have been obvious to the ordinary artisan. Cullmann
teaches “the use of carbohydrate-cleaving enzymes for prophylaxis and
treatment of cardiovascular diseases” (Cullmann 2). Cullmann also teaches
that hyaluronidase is especially suitable as a carbohydrate-cleaving enzyme
(id. at 2-3).
Cullmann exemplifies treating “[n]umerous patients with
cardiovascular complaints . . . [o]ver several weeks (generally at least 2
weeks)” by intravenously administering hyaluronidase (id. at 4). Cullmann
exemplifies dosages of “1500 units … three times per week,” as well as “a
range from 3 x 3000 units per week to a dose of 3 x 4500 units per week,
whereby up to 4500 units maximum per day were administered” (id. at 5).
Johnsson teaches using hyaluronidase to treat “inflammation
associated with an increased local synthesis of hyaluronan,” and that “an
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increased concentration of hyaluronan has been shown in tissue . . .
characterized by a condition of inflammatory-immunological injury such as
… myocardial infarction” (Johnsson 1). Johnsson also teaches that
appropriate daily dosages of hyaluronidase range from “1 to 80000 IU of
hyaluronidase/kg/body weight of said mammal, more preferably from 100
IU to 20000 IU by kg of the body weight by local or systemic
administration” (id. at 5). Johnsson exemplifies administering “daily
injections of hyaluronidase 20000 IU/kg bw/day” intravenously to rats (id. at
5-6).
We agree with Examiner it would have been prima obvious to one of
skill in the art at the time the invention was made to combine the teachings
of Cullmann and Johnsson and thereby arrive at the method defined by claim
7. Specifically, Cullmann teaches treating cardiovascular disease by
administering hyaluronidase over a period of several weeks in dosages up to
4500 units three times per week. The method of claim 7 differs from
Cullmann in that claim 7 requires at least 6000 units per day. However,
Johnsson teaches administering hyaluronidase in daily dosages of up to
80,000 units per kilogram body weight to treat conditions including
myocardial infarction. We conclude that the teachings of Cullmann and
Johnsson would have made it obvious to administer hyaluronidase to treat
cardiovascular disease by administering at least 6000 units per day of
hyaluronidase for at least four weeks, as required by claim 7.
Appellants argue that there is no motivation to combine the cited
references and arrive at the invention of claim 7 because Johnsson discloses
a hyaluronidase-based treatment of graft-induced inflammation, which is a
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disease completely distinct from the cardiovascular disease recited in claim
7 (Br. 3). Appellants argue that there is no motivation to combine different
dosage regimens across unrelated diseases since dosage regimens have to be
adapted to the needs of particular diseases (id. at 3-4).
We are not persuaded by this argument. As discussed above,
Johnsson teaches the use of hyaluronidase for the treatment of inflammation
associated with an increased local synthesis of hyaluronan and that an
increased concentration of hyaluronan results from inflammatory-
immunological injury such as myocardial infarction. The fact that Johnsson
exemplifies the use of hyaluronidase for the treatment of transplantation
does not detract from the general teaching in Johnsson of the use of
hyaluronidase for the treatment of inflammation associated with an increased
local synthesis of hyaluronan, including myocardial infarction.
Appellants further argue that the cited references do not provide a
reasonable expectation of success because Appellants have demonstrated
that the therapeutic method disclosed in Cullmann is unsuccessful in treating
cardiovascular disease (Br. 5-6, citing the Declaration of Heinz Dieter
Cullmann dated Jan. 11, 2006). In particular, Appellants argue that “the
Cullman Declaration demonstrates a hyaluronidase treatment for
cardiovascular disease which employs the dosage regimen disclosed in the
Cullman patent, i.e. 3 x 1,500 units of hyaluronidase per week to 3 x 4,500
units hyaluronidase per week, . . . resulted in a success rate of only 13% and
only a sporadic improvement in the pathological state…” (Br. 5-6.)
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Appellants further argue that Storch3 “provides further evidence that one of
ordinary skill in the art would not have a reasonable expectation of success”
in making the invention defined by claim 7 because Storch illustrates that
“one of ordinary skill in the art was well aware of the considerable risk
associated with administration of high doses of hyaluronidase” (id. at 7).
We are not persuaded by this argument. The Cullmann declaration
does not describe what treatment protocols were followed and what
measures were defined as successful treatment. Even assuming the data
support the assertions in the Cullmann declaration, however, they would not
rebut the Examiner’s rejection. The relevant question is whether those of
ordinary skill would have reasonably expected to be successful in modifying
Cullmann’s method as suggested by Johnsson; specifically, by increasing the
dosages of hyaluronidase. The data attached to the Cullmann declaration do
not show that those of ordinary skill would have doubted the success of the
method suggested by the combined references.
Neither does the Storch reference.4 The Storch reference concludes
that while “26 per cent of human patients developed antibodies after
application of Hylase®” (i.e. hyaluronidase), “[n]o anaphylactic reactions
were observed in 17 patients with antibodies when intravenous application
of hyaluronidase was continued” (Storch 133). Storch does not support
Appellants’ position that those skilled in the art would have doubted the
success of the method suggested by Cullmann and Johnsson. Thus, given

3 Storch et al., 11 Z. Exper. Chirurg. 128-133 (1978).
4 Most of the Storch reference is in German. We have considered only the
English-language abstract.
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the explicit teaching of Cullman that hyaluronidase is especially suitable for
treatment of cardiovascular disorders and given that the instantly claimed
dosage is well within the dosage range that is taught by Johnsson as being
suitable for human therapeutics and the treatment of cardiovascular
conditions such as myocardial infarction, we agree with the Examiner that
one of skill in the art would have had a reasonable expectation of success in
practicing the claimed method.
Appellants further argue that they have rebutted any prima facie case
of obviousness with objective evidence of nonobviousness (Br. 7).
Appellants argue that “a study of 120 patients with coronary heart disease
that were treated with hyaluronidase in accordance with the presently
claimed invention” showed a success rate of more that 95% (citing Exhibit
A of the Cullmann Declaration ) (id. at 8).
We are not persuaded by this argument. “Consistent with the rule that
all evidence of nonobviousness must be considered when assessing
patentability, the PTO must consider comparative data in the specification in
determining whether the claimed invention provides unexpected results. . . .
However, ‘it is well settled that unexpected results must be established by
factual evidence. Mere argument or conclusory statements in the
specification does not suffice.’” In re Soni, 54 F.3d 746, 750 (Fed. Cir.
1995).
Here, Appellants’ unexpected results argument is not supported by
factual evidence. The Cullmann Declaration itself does not refer to any
results obtained in treating patients with the claimed dosage of at least 6,000
units per day of hyaluronidase for at least four weeks. Nor does the
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attachment to the declaration explain how the 120 patients were treated.
Neither the declaration nor the attachment explains the meaning of the
graphs in the attachment. Finally, the declaration does not assert that any of
the results were unexpected. Appellants’ brief asserts that various results
were found in the study and that some of them were surprising, but attorney
argument is not evidence. See In re Pearson, 494 F.2d 1399, 1405 (CCPA
1974). Because we find that no factual evidence of unexpected results has
been provided, we conclude that the prima facie case of obviousness has not
been overcome by a showing of unexpected results.
3. OBVIOUSNESS II
Claims 7-31 stand rejected under 35 U.S.C. § 103 as obvious in view
of Cullmann, Johnsson, Cavazza US, 5 Cavazza WO, 6 Al-Zuhair7, and
Littera.8 Claims 8-31 have not been argued separately and therefore stand or
fall with claim 7. 37 C.F.R. § 41.37(c)(1)(vii).
The Examiner relies on Cullmann and Johnsson for the disclosures
discussed above and relies on the other cited references to meet limitations
found in dependent claims (Answer 6). Since claims 8-31 stand or fall with
claim 7, we find it unnecessary to discuss the teachings of Cavazza US,
Cavazza WO, Al-Zuhair, and Littera. Cullmann and Johnsson support a
prima facie case of obviousness with respect to claim 7, as discussed above.

5 Cavazza, US 4,743,621, May 10, 1988
6 Cavazza, WO 99/01126, Jan. 14, 1999
7 Al-Zuhair et al., Pharmacological Research, Vol. 38, No. 1, 1998, pp. 65-
72.
8 Littera, EP 561744, Sept. 22, 1993
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Appellants argue that the disclosures of Cavazza US, Cavazza WO,
Al-Zuhair, and Littera do not compensate for the deficiencies of the
combination of the Cullmann patent and the Johnsson reference in disclosing
the claimed invention (Br. 15).
For the reasons discussed above, however, we agree with the
Examiner that Cullmann and Johnsson would have made obvious the
method of claim 7 to those of ordinary skill in the art. We therefore affirm
the rejection based on the combination of Cullmann, Johnsson, Cavazza US,
Cavazza WO, Al-Zuhair, and Littera. Claims 8-31 fall with claim 7.
SUMMARY
The Examiner’s rejections are supported by the preponderance of the
evidence of record. We therefore affirm the rejection of claims 7-31 under
35 U.S.C. § 103.
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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