Ex Parte Coolidge et al

Board of Patent Appeals and Interferences

Sep 17, 2010

11007938 (B.P.A.I. Sep. 17, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
11/007,938 12/08/2004 Thomas R. Coolidge 0211-DIV-9 4875
44638 7590 09/20/2010
Intellectual Property Department
Amylin Pharmaceuticals, Inc.
9360 Towne Centre Drive
San Diego, CA 92121
EXAMINER
HA, JULIE
ART UNIT PAPER NUMBER
1654
MAIL DATE DELIVERY MODE
09/20/2010 PAPER
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte THOMAS R. COOLIDGE and MARIO EHLERS
__________

Appeal 2010-004050
Application 11/007,938
Technology Center 1600
__________

Before TONI R. SCHEINER, DONALD E. ADAMS, and DEMETRA J. MILLS,
Administrative Patent Judges.

SCHEINER, Administrative Patent Judge.

DECISION ON APPEAL1
This is an appeal under 35 U.S.C. § 134 from the final rejection of
claims 37-40 and 42-45. The claims have been rejected as obvious. We
have jurisdiction under 35 U.S.C. § 6(b).

1 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, or for filing a request for rehearing,
as recited in 37 C.F.R. § 41.52, begins to run from the “MAIL DATE”
(paper delivery mode) or the “NOTIFICATION DATE” (electronic delivery
mode) shown on the PTOL-90A cover letter attached to this decision.

Appeal 2010-004050
Application 11/007,938
2
STATEMENT OF THE CASE
According to the Specification, “[p]atients with diabetes are at high
risk for developing diabetic cardiomyopathy (DCM)” (Spec. 2: 25). “High
levels of catecholamines, such as norepinephrine, in the heart or circulation
result in the development of DCM” (id. at 3: 7-8).
“Administration of GLP-1 [glucagon-like peptide-1] has been found
unexpectedly to suppress plasma blood levels of norepinephrine” and “will
be useful in reducing norepinephrine levels in the heart and/or plasma that
are associated with the development of diabetic cardiomyopathy” (id. at 3:
15-21). “Preferred GLP-1 molecules of the invention include GLP-1(7-36)
amide, GLP-1(7-37), [exendin-3] and exendin-4” (id. at 4: 4-5; 12: 1-20).
Claims 37, 38, and 43-45 are representative of the subject matter on
appeal:
37. A method for treating diabetic cardiomyopathy in a patient in
need thereof comprising administering to said patient an amount of an
exendin effective to treat diabetic cardiomyopathy in said patient.

38. The method according to claim 37, wherein said amount of said
exendin is effective to cause a reduction in plasma or heart norepinephrine
levels.

43. The method according to claim 37, wherein said exendin is
administered at a dose of about 0.1 pmol/kg/min.2

2 Claims 43-45 in the Appendix accompanying Appellants’ Appeal Brief
mistakenly depend from claim 41. However, claim 41 was canceled, and
claims 43-45 were amended to depend from claim 37 in an amendment filed
after final on November 6, 2008. The Examiner indicated that the
amendment would be entered on appeal in an Advisory Action dated
November 25, 2008.
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Application 11/007,938

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44. The method according to claim 37, wherein said exendin is
administered subcutaneously at a dose of from about 0.5 pmol/kg/min to
about 50 pmol/kg/min.

45. The method according to claim 37, wherein said exendin is
administered intravenously at a dose of from about 0.1 pmol/kg/min to about
10 pmol/kg/min.

Claims 37-40 and 42-45 stand rejected under 35 U.S.C. § 103(a) as
unpatentable over Treadway3 in view of Eng4 and Fein.5
We affirm.

ISSUE
Does a preponderance of the evidence of record support the
Examiner’s conclusion that it would have been obvious to administer an
exendin to a patient with diabetic cardiomyopathy, in an amount effective to
treat diabetic cardiomyopathy?

FINDINGS OF FACT (FF)
1. Treadway teaches that “[d]iabetic cardiomyopathy occurs in
patients having insulin dependent diabetes mellitus (Type 1) and in patients
having non-insulin dependent diabetes mellitus (Type 2)” (Treadway, col. 1,
ll. 35-38).
2. Treadway discloses treating diabetic cardiomyopathy by
administering a glycogen phosphorylase inhibitor alone, “or in combination

3 U.S. Patent 6,867,184 B2, issued March 15, 2005.
4 U.S. Patent 5,424,286, issued June 13, 1995.
5 Frederick S. Fein, Diabetic Cardiomyopathy, 13 DIABETES CARE 1169-
1179 (1990).
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Application 11/007,938

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with other pharmaceutically active compounds . . . intended to treat the same
disease or condition as the glycogen phosphorylase inhibitor or a different
disease or condition” (Treadway, col. 27, ll. 8-12), notably, “agents used to
treat diabetes such as insulin and insulin analogs (e.g., LysPro insulin);
GLP-1 (7-37) (insulinotropin) and GLP-1 (7-36)-NH2” (id. at col. 33, ll. 61-
65).
3. “Also contemplated for use in combination with a glycogen
phosphorylase inhibitor are pramlintide acetate (SymlinTM), AC2993, and
nateglinide” (Treadway, col. 34, ll. 15-18).
4. There is no dispute that AC2993 is the same as exendin 4 (Ans.
3, 10; Reply Br. 2).
5. Treadway recommends dosages of glycogen phosphorylase
inhibitors for treating diabetic cardiomyopathy (Treadway, col. 29, l. 58 to
col. 30, l. 3), but does not discuss dosages for any of the other agents to be
used in combination with the glycogen phosphorylase inhibitors.
6. Eng discloses pharmaceutical compositions containing exendin-
3 and/or exendin-4 which “ha[ve] the advantage of being more potent than
other insulinotropic peptides” for “the treatment of diabetes mellitus” (Eng,
col. 2, ll. 37-60).
The compositions . . . will normalize hyperglycemia
through glucose-dependent, insulin-dependent and insulin-
independent mechanisms. Therefore they will be useful as
primary agents for the treatment of type II diabetes mellitus and
as adjunctive agents for the treatment of type I diabetes
mellitus.
(Id. at col. 2, ll. 41-48.)

Appeal 2010-004050
Application 11/007,938

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7. Eng teaches that:
The use of exendin-3 and [exendin-]4 in compositions
that may be injected intravenously, intramuscularly,
subcutaneously, or intraperitoneally, would call for dosages of
about 0.1 pg/kg to 1,000 mg/kg body weight depending on
many individual factors such as age, severity of disease, total
body weight, sex and other mitigating factors.
(Eng, col. 5, ll. 13-19.)
8. The Examiner finds, and Appellants do not dispute, that the
MW of exendin is 4186.57 g/mol, therefore, 0.1 mg/kg/day is equal to about
16 pmol/kg/min (Ans. 4, 5). The Examiner further finds, and Appellants do
not dispute, that Eng’s exendin dosage of “0.1 pg/kg to 1000 mg/kg . . .
would include the [instantly required dosage of] 0.1 pmol/kg/min to about
50 pmol/kg/min, since about 0.001 mg/kg/day would yield about 0.1
pmol/kg/min” (id. at 5).
9. Fein teaches that “[d]iabetes is associated with the development
of cardiomyopathy,” and [d]iabetic cardiomyopathy is a significant cause of
heart failure in diabetic subjects” (Fein, Abstract).
10. The Specification teaches that “GLP-1 [molecules] will be
useful in reducing norepinephrine levels in the heart and/or plasma that are
associated with the development of diabetic cardiomyopathy” (Spec. 3: 15-
21), and “‘GLP-1 molecules’ of the present invention” include exendin 3
and exendin 4 (Spec. 12: 1-20).
11. The Specification discloses that “[a]dministration of a GLP-1
molecule may be as soon as . . . DCM [diabetic cardiomyopathy] is
diagnosed, and the administration can be either continuous or on an
intermittent basis, for as long as necessary” (Spec. 14: 16-18). In addition:
Appeal 2010-004050
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The amount of a GLP-1 molecule that should be
administered will vary according to the severity of the
conditions and the patient. . . . For intravenous administration, a
typical dose of a GLP-1 molecule will be 1.5 pmol/kg/min. The
range of the dose may vary between about 0.1-10 pmol/kg/min.
For subcutaneous administration, the optimal dose is 5
pmol/kg/min, with a range between about 0.5-50 pmol/kg/min.
(Id. at 14: 21-28.)
DISCUSSION
We agree with Appellants that “Treadway discloses exendin-4 for
treating the co-morbidity of diabetes, and not for treating diabetic
cardiomyopathy” and that “Treadway does not disclose or suggest the
treatment of diabetic cardiomyopathy by the administration of exendin”
(Reply Br. 2). We also agree with Appellants that Treadway discloses that
glycogen phosphorylase inhibitors can be administered “with a very large
number” of compounds “for treating different problems and/or conditions.
But it clearly does not follow that each of these compounds are also useful
for treating diabetic cardiomyopathy” (Suppl. App. Br. 5).6 Finally, we
agree with Appellants that “[n]one of the references cited disclose or suggest
an effect on norepinephrine levels” (id. at 6).
Nevertheless, Appellants’ arguments don’t address the salient issue in
this case - whether one of skill in the art would have had a reason to
administer an exendin to a patient with diabetic cardiomyopathy, and if so,
whether the amount of exendin would have been effective (on its own) to
treat cardiomyopathy and/or reduce norepinephrine levels. As long as some
suggestion to combine the elements is provided by the prior art as a whole,

6 Dated March 31, 2009.
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the law does not require that they be combined for the reason or advantage
contemplated by the inventor. See e.g., In re Beattie, 974 F.2d 1309, 1312
(Fed. Cir. 1992); In re Kronig, 539 F.2d 1300, 1304 (CCPA 1976).
We agree with the Examiner’s conclusion that it would have been
obvious for one of ordinary skill in the art to administer an exendin, along
with a glycogen phosphorylase inhibitor,7 to patients with diabetic
cardiomyopathy, given the Examiner’s uncontroverted findings that patients
with diabetic cardiomyopathy are also patients with type I or type II diabetes
mellitus (Ans. 5, 11; FF1, FF9); patients with diabetic cardiomyopathy (i.e.,
patients with underlying type I or type II diabetes) can be treated with a
glycogen phosphorylase inhibitor in combination with “agents used to treat
diabetes,” including exendin 4 (Ans. 3; FF2-5); and it is conventional to treat
patients with type I or type II diabetes with exendin-3 and/or exendin-4
(Ans. 4; FF6).
With respect to the amount of exendin 3 and/or 4 to be administered,
Appellants do not dispute the Examiner’s finding that Eng’s suggested dose
of exendin overlaps with the dose asserted in the Specification to be
effective in treating cardiomyopathy (FF8). Moreover, Appellants have not
argued or otherwise established that the same levels would not be effective
for reducing norepinephrine levels. Therefore, we find no error in the
Examiner’s conclusion that administering an exendin (in combination with a
glycogen phosphorylase inhibitor) to a patient with diabetic cardiomyopathy
(i.e., a patient with underlying diabetes) in an amount effective for treating

7 The claims use the open transitional term “comprising,” and therefore
don’t preclude administration of an exendin in combination with another
pharmaceutical compound.
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diabetes, would also be effective for treating diabetic cardiomyopathy and
reducing norepinephrine levels.
CONCLUSION
The evidence of record supports the Examiner’s conclusion that it
would have been obvious to administer an exendin to a patient with diabetic
cardiomyopathy, in an amount effective to treat diabetic cardiomyopathy.
The rejection of claims 37-40 and 42-45 under 35 U.S.C. § 103(a) as
unpatentable over Treadway in view of Eng and Fein is affirmed.

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)(1)(iv)(2006).

AFFIRMED

cdc

INTELLECTUAL PROPERTY DEPARTMENT
AMYLIN PHARMACEUTICALS, INC.
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