Ex Parte Coolidge et al

Board of Patent Appeals and Interferences

Apr 22, 2010

11255279 (B.P.A.I. Apr. 22, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte THOMAS R. COOLIDGE and MARIO EHLERS
__________

Appeal 2009-012058
Application 11/255,279
Technology Center 1600
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Decided: April 23, 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 54, 55, and 57-59.1 We have
jurisdiction under 35 U.S.C. § 6(b).

1 Claims 28, 48, 50-53, 56, and 60-65 are also pending, but stand withdrawn
from consideration.

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Application 11/255,279

STATEMENT OF THE CASE
Claim 54 is representative of the claims on appeal, and reads as
follows:
54. A method for treatment of a patient suffering from one or more
conditions selected from group consisting of unstable angina, non-Q-wave
cardiac necrosis, Q-wave myocardial infarction, acute myocardial infarction,
ischemic heart disease, and stable angina, comprising
administering to said patient an amount of an exendin therapeutically
effective to treat unstable angina, non-Q-wave cardiac necrosis, Q-wave
myocardial infarction, acute myocardial infarction, ischemic heart disease,
or stable angina,
wherein said administration is after the onset of one or more of the
following symptoms: chest pain lasting longer than 15 minutes, chest pain at
rest, chest pain following minimal exertion, nausea, shortness of breath,
palpitations, or dizziness.

The Examiner relies on the following evidence:
Eng US 5,424,286 Jun. 13, 1995
Efendic US 6,277,819 B1 Aug. 21, 2001
Levine et al. US 6,448,045 B1 Sept. 10, 2002

Barragàn et al., Interactions of exendin-(9-39) with the effects of glucagon-
like peptide-1-(7-36) amide and of exendin-4 on arterial blood pressure and
heart rate in rats, 67 REGULATORY PEPTIDES 63-68 (1996).

We affirm.

ISSUE
Does the evidence of record support the Examiner’s conclusion that it
would have been obvious to use exendin-4 as taught by Levine, Eng, and
Barragán for the GLP-1 analog in the method of Efendic?

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FINDINGS OF FACT
FF1 According to the Specification, the invention is drawn to methods “for
the treatment of acute coronary syndrome, particularly unstable angina and
non-Q-wave cardiac necrosis, with a GLP-1 molecule.” (Spec. 5.)
FF2 The Specification teaches further that the term GLP-1 molecule
includes GLP-1, GLP-1 peptides, as well as biologically active variants,
analogs, and derivatives of GLP-1 peptides. (Id. at 8-9.)
FF3 The Examiner rejects claims 54, 55, and 57-59 under 35 U.S.C. §
103(a) as being rendered obvious by the combination of Efendic, Levine,
Eng, and Barragán. (Ans. 3.) As Appellants do not argue the claims
separately, we focus our analysis on claim 54, and claims 55 and 57-59 stand
or fall with that claim. 37 CFR § 41.37(c)(1)(vii).
FF4 The Examiner finds that “Efendic discloses a method of treating a
patient who has suffered an acute myocardial infarction (MI), particularly a
diabetic patient, by administering a therapeutically effective amount of GLP-
1, a GLP-1 analog or a GLP-1 derivative, to normalize blood glucose.” (Id.)
FF5 Efendic relates “to a method of reducing mortality and morbidity after
myocardial infarction in diabetic patients.” (Efendic, col. 1, ll. 10-12.)
FF6 In the method of Efendic, GLP-1, GLP-1 analogs, GLP-1 derivatives,
and pharmaceutically-acceptable salts thereof, are administered to a patient
in need thereof at a dose effective to normalize blood glucose. (Id. at col. 3,
ll. 13-18.)
FF7 In Example 1 of Efendic, patients with non-insulin dependent diabetes
were administered GLP-1, and then, as a control, the same patients were
infused with insulin on a different day than the GLP-1 infusion. (Id. at col.
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12-13, Example 1.) Efendic found that the “metabolic control with GLP-1
(7-36) amide was better than that achieved by insulin.” (Id. at col. 13, ll. 9-
10.)
FF8 In Example 2 of Efendic, patients with non-insulin dependent diabetes
were infused with GLP-1 for three hours during breakfast, lunch, and dinner,
and then, as a control, the same patients were injected with insulin before the
start of the meals on a different day than the GLP-1 infusion. (Id. at col. 13,
Example 2.) Efendic found that “GLP-1 (7-36) amide infusion more
effectively controls post-prandial glucose levels than insulin injection, and
that the control is effective as long as GLP-1 (7-36) amide infusion is
continued.” (Id. at col. 14, ll. 7-10.)
FF9 In the Examples, Efendic did not co-administer insulin and glucose
with the GLP-1 (7-36) amide.
FF10 The Examiner notes that “Efendric does not disclose that one of the
analogs or derivatives of GLP-1 is exendin-4.” (Ans. 4.)
FF11 The Examiner cites Levine for teaching that “exendin-4 is an analog
of GLP-1 that binds to GLP-1 receptors and induces insulin expression.”
(Id.) The Examiner thus finds that “Levine et al. teach[es] that GLP-1 and
exendin-4 are functional equivalents with respect to stimulating insulin
production from pancreatic β-cells.” (Id.)
FF12 Levine teaches that “[i]nduction of β-cell differentiation in cultured
human β-cells was achieved by stimulating multiple signaling pathways,
including those downstream of the homeodomain transcription factor PDX-
1, cell-cell contact, and the glucagon-like peptide-1 (GLP-1) receptor.”
(Levine, col. 2, ll. 16-20.)
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FF13 Levine teaches that insulin gene expression may be induced in
cultured endocrine pancreas cells by expressing a PDX-1 gene in cultured
cells that are in contact with other cells in the culture, and contacting the
cells with a GLP-1 receptor agonist. (Id. at col. 2, ll. 29-36.)
FF14 Levine further teaches that the GLP-1 receptor agonist may be GLP-1,
exendin-3, and exendin-4. (Id. at col. 2, ll. 58-61.) “Cells are contacted with
a GLP-1 receptor agonist in a time and amount effective to induce insulin
mRNA expression.” (Id. at col. 5, ll. 20-35.)
FF15 The Examiner finds that “Eng discloses that exendin-4 is more potent
than GLP-1 in stimulating insulin production.” (Ans. 4.)
FF16 Specifically, Eng teaches compositions containing exendin-3 or
exendin-4, wherein the compositions normalize hyperglycemia through
glucose-dependent, insulin-dependent and insulin-independent mechanisms.
(Eng, col. 2, ll. 37-43.) Eng teaches that the compositions may be used for
the treatment of diabetes and the prevention of hyperglycemia and identifies
exendin-4 as an insulinotropic agent. (Id. at col. 2, ll. 37-48.)
FF17 The Examiner cites Barragán for teaching that exendin-4 and GLP-1
are functional equivalents, as they bind to the same receptors and produce
the same chemical mediators biological effects. (Ans. 4.) The Examiner
finds that Barragán also teaches that “exendin-4 is more stable and has a
longer in vivo half-life and/or higher receptor affinity, as it binds to GLP-1
receptors for a longer period of time.” (Id.)
FF18 Barragán determined “the interactions of peptide exendin-(9-39) with
the effect of glucagon-like peptide-1-(7-36) (GLP-1 (7-36)) amide and of
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exendin-4 on arterial blood pressure and heart rate in the rat.” (Barragán,
Abstract.)
FF19 Barragán found that “[b]oth GLP-1 (7-36) amide and exendin-4
produced a dose-dependent increase in systolic, diastolic and mean arterial
blood pressure, as well as in heart rate, although the effect of exendin-4 was
more prolonged,” suggesting “a longer functional half-life in vivo for
exendin-4 as compared to GLP-1.” (Id.)
FF20 According to Barragán, exendin-4, like GLP-1 (7-36) amide, “has a
pronounced effect on the production of cyclic AMP and stimulates glucose-
induced insulin secretion by pancreatic rat islets.” (Id. at 64, first column.)
Barragán teaches further that exendin-4 “competes with GLP-1 (7-36) amide
on the same binding sites, as well as producing the same chemical mediator
and biological effects.” (Id. at 67, first column.)
FF21 Barragán thus teaches:
At this point, there are important differences between the
beneficial actions of GLP-1 (7-36) amide and of exendin-4 on
insulin release and insulin-like effects on peripheral tissues, and
the undesirable effects of these peptides on arterial blood
pressure and heart rate, which should be dangerous to be
induced in diabetic patients. Then, changes on cardiovascular
parameters, and on brain physiology, water balance and body
temperature . . . induced by those peptides in experimental
animals must be also tested in men, in order to establish the
criteria for their use as potential therapeutic agents.

(Id. at 68, first column.)
FF22 The Examiner concludes:
It would have been obvious to one of ordinary skill in the
art at the time that the invention was made to replace GLP-1
with exendin-4 in the method of Efendic (to regulate glucose
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and insulin following a heart attack in order to minimize cardiac
damage), because Barragán et al. and Levine et al. disclose that
the two polypeptides are functional equivalents, because
Barragán et al. disclose that exendin-4 is more stable and
longer-acting in vivo compared to GLP-1, and because Eng
discloses that exendin-4 is a stronger agent for stimulating
insulin production than GLP-1.

(Ans. 4.)

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).
In KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 415 (2007), the
Supreme Court rejected a rigid application of a teaching-suggestion-
motivation test in the obviousness determination. The Court emphasized
that “the [obviousness] analysis need not seek out precise teachings directed
to the specific subject matter of the challenged claim, for a court can take
account of the inferences and creative steps that a person of ordinary skill in
the art would employ.” Id. at 418. See also id. at 421 (“A person of
ordinary skill is also a person of ordinary creativity, not an automaton.”).
Thus, an “[e]xpress suggestion to substitute one equivalent for another need
not be present to render such substitution obvious.” In re Fout, 675 F.2d
297, 301 (CCPA 1982).
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Moreover, it is well-recognized that merely discovering and claiming
a new benefit of an old process cannot render the process again patentable.
In re Woodruff, 919 F.2d 1575, 1577-78 (Fed. Cir. 1990); Bristol-Myers
Squibb Co. v. Ben Venue Laboratories, Inc., 246 F.3d 1368, 1376 (Fed. Cir.
2001) (“Newly discovered results of known processes directed to the same
purpose are not patentable because such results are inherent.”).

ANALYSIS
Appellants argue that “while Efendic discloses GLP-1 for the
normalization of blood glucose in patients in the acute phase of myocardial
infarction and who are incapable of auto-regulation of blood glucose, it does
not disclose GLP-1 in the treatment of a patient suffering from myocardial
infarction regardless of their ability to auto-regulate blood glucose.” (App.
Br. 6-7.) Specifically, Appellants assert, “Efendic does not disclose direct
treatment of the underlying myocardial infarction.” (Id. at 7.) Thus,
Appellants assert, the Examiner has not considered the Efendic reference as
a whole, and has relied on improper hindsight in formulating the rejection.
(Id. at 7-8.)
Appellants’ arguments have been considered, but are not convincing.
As noted by the Examiner (Ans. 7), Appellants’ claims do not exclude
diabetic patients, and Efendic teaches a method of reducing mortality and
morbidity after myocardial infarction in diabetic patients by administering
GLP-1 or a GLP-1 analog. While Efendic does not teach the direct
treatment of myocardial infarction, Efendic teaches treatment of diabetic
patients suffering from myocardial infarction, a subset of patients
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encompassed by the claimed patient population, with a GLP-1 analog, to
reduce mortality and morbidity after myocardial infarction.
Appellants argue further that Levine and Barragán do not establish
that GLP-1 and exendin-4 are “‘functional equivalents.’” (App. Br. 8.) As
to Levine, Appellants argue that Levine notes that exendin-4 by itself did not
have any effect on hormone expression in βlox5 cells, and that “[i]t was only
when βlox5 cells were grown in cells expressing PDX-1 in suspension
cultures as 3-dimensional aggregates that the presence of exendin-4 induced
insulin production.” (Id.) Thus, Appellants assert, it required three factors,
i.e., PDX-1, cell-cell contact, and exendin-4, to induce insulin production.
(Id.) Moreover, Appellants assert, Efendic also co-administers insulin and
glucose, whereas the objective of Levine is to induce insulin production.
(Reply Br. 2.) Thus, Appellants assert, “it is illogical to assert that a person
of ordinary skill would use the exendin-4 disclosed by Levine as a GLP-1
analog in the method of Efendic in order to achieve insulin production when
insulin is already co-administered in the method of Efendic.” (Id.)
As to Barragán, Appellants assert that while the reference teaches that
exendin-4 is an agonist “of GLP-1 (7-36) amide on both arterial blood
pressure and heart rate,” that would “not lead a person of ordinary skill in
the art to conclude that exendin-4 and GLP-1 (7-36) are functional
equivalents, much less functional equivalents in every context.” (App. Br.
8-9.) Appellants argue further as to Barragán that Barragán teaches that
exendin-4 produces an increase in arterial blood pressure and heart rate, and
thus the ordinary artisan would not administer a composition comprising
exendin-4 to a patient suffering a heart attack. (Reply Br. 2-3.) According
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to Appellants, Barragán in fact teaches “that administration of exendin-4 to
diabetic patients would be dangerous.” (Id. at 3 (citing Barragán, p. 68, left
column).)
Appellants’ arguments are not found to be convincing. As discussed
above, Efendic teaches a method of reducing mortality and morbidity after
myocardial infarction in diabetic patients by administering GLP-1 or a
GLP-1 analog to normalize blood glucose. Efendic therefore teaches a
method that encompasses the method of claim 54. Efendic differs from the
method of claim 54 by failing to specifically teach that the GLP-1 analog is
exendin-4. Levine, Eng, and Barragán teach that exendin-4 is a GLP-1
receptor agonist having insulinotropic properties. Thus, we agree with the
Examiner that it would have been obvious to the ordinary artisan to use
exendin-4 as the GLP-1 analog in the method of Efendic.
As to Appellants’ argument that Levine teaches that three factors were
required, PDX-1, cell-cell contact, and exendin-4, to induce insulin
production, those factors were required in cell culture. Eng, however,
teaches that compositions containing exendin-4 may be used for the
treatment of diabetes and the prevention of hyperglycemia. As to
Appellants’ arguments regarding Barragán, while Barragán does teach that
exendin-4 produces an increase in arterial blood pressure and heart rate,
Barragán teaches that GLP-1 also produced a dose-dependent increase in
systolic, diastolic and mean arterial blood pressure, as well as in heart rate,
although the effect of exendin-4 was more prolonged. As to Barragán’s
teaching that the use of exendin-4 may be dangerous in diabetic patients, we
again note that Eng specifically teaches that compositions containing
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exendin-4 may be used in the treatment of diabetic patients. All that is
required is a reasonable expectation of success, not absolute predictability of
success. In re O’Farrell, 853 F.2d 894, 903 (Fed. Cir. 1988). We note
further that Appellants have not presented any arguments as why Eng does
not support the Examiner’s conclusion that it would have been obvious to
the ordinary artisan to use exendin-4 as the GLP-1 analog in the method of
Efendic. Arguments not made are waived. See 37 C.F.R. § 41.37(c)(1)(vii).

CONCLUSION OF LAW
We conclude that the evidence of record supports the Examiner’s
conclusion that it would have been obvious to use exendin-4 as taught by
Levine, Eng, and Barragán for the GLP-1 analog in the method of Efendic.
We thus affirm the rejection of claims 54, 55, and 57-59 under 35
U.S.C. § 103(a) as being rendered obvious by the combination of Efendic,
Levine, Eng, and Barragán.

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

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