Ex Parte Ehrich

Board of Patent Appeals and Interferences

Apr 1, 2011

10635233 (B.P.A.I. Apr. 1, 2011)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte ELLIOT EHRICH
__________

Appeal 2010-008384
Application 10/635,233
Technology Center 1600
__________

Before TONI R. SCHEINER, ERIC GRIMES, 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 a method
of improving drug delivery in a patient. The Examiner has rejected the
claims as obvious in view of the prior art. We have jurisdiction under 35
U.S.C. § 6(b). We affirm.
STATEMENT OF THE CASE
The Specification discloses that “[p]olymorphic cytochrome P450
(CYP) has been identified as being important in the metabolism of many
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drugs.… Individuals have been genotypically classified as ultra rapid
metabolizers (UM), carrying an extra CYP 2D6 gene, homozygous extensive
metabolizers (EM) and heterozygous EM and poor metabolizers (PM).”
(Spec. 1: 5-11.) The Specification discloses that “injecting extended release
formulations creates an unexpected advantage in treating patients classified
as CYP 2D6 UM and/or EM” (id. at 1: 21 to 2: 1); i.e., “individuals who
possess a functional CYP 2D6 gene” (id. at 6: 18).
Claims 1-7, 10, 11, and 13-20 are on appeal. The claims have not
been argued separately and therefore stand or fall together. 37 C.F.R.
§ 41.37(c)(1)(vii). Claim 1 is representative and reads as follows:
1. A method of improving drug delivery in a patient possessing a
functional CYP2D6 gene comprising injecting or implanting a
therapeutically effective amount of an active agent that is metabolized by
CYP2D6 in a first extended release formulation in a first administration
wherein the first extended release formulation releases the active agent over
a period of at least about 7 days and further comprising administering an
inhibiting agent that inhibits CYP2D6 in an inhibiting amount wherein the
inhibiting agent is not the active agent.

Issue
The Examiner has rejected all of the claims on appeal under 35 U.S.C.
§ 103(a) as being obvious in view of Oshiro,1 STN,2 Vandel,3 Bymaster,4
and Ramstack.5

1 Oshiro et al., US 5,006,528, Apr. 9, 1991
2 STN Registry File No. 129722-12-9 Aripiprazole, Retrieved from STN
2007-06-307.
3 P. Vandel et al., Drug extrapyramidal side effects. CYP2D6 genotypes and
phenotypes, 55 EUR. J. CLIN. PHARMACOL., 659-665 (1999)
4 Bymaster et al., US 6,147,072, Nov. 14, 2000
5 Ramstack et al., US 5,650,173, July 22, 1997
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The Examiner finds that Bymaster discloses “serotonin reuptake
inhibitors, such as, e.g., fluoxetine … in combination with an atypical
antipsychotic agent … for use in the treatment of psychotic conditions, such
as, e.g., schizophrenia” (Answer 6). The Examiner finds that Oshiro
discloses a compound that is useful for the treatment of schizophrenia (id. at
4), which, as shown by STN, is known as aripiprazole (id. at 5). The
Examiner finds that Ramstack discloses “microparticles containing a
biologically active agent” (id.) as an injectable system that can provide
extended release of an active agent for, “e.g., 30-200 days” (id. at 6).
The Examiner concludes that one of ordinary skill in the art would
have found it obvious to employ Ramstack’s injectable microparticles to
administer aripiprazole in order “to extend the duration of action of a drug
over an extended period of time” (id.). The Examiner concludes that one of
ordinary skill in the art would have found it obvious to combine Oshiro’s
aripiprazole with Bymaster’s fluoxetine because both compounds were used
in the treatment of schizophrenia (id. at 7). The Examiner also finds that
Vandel discloses that “90-95% of at least Caucasian individuals possess a
functional CYP2D6 gene” (id. at 8), and therefore treatment with Oshiro’s
aripiprazole “would necessarily encompass its use in subjects possessing a
functional CYP2D6 gene” (id.).
Appellant contends that the Examiner erred in finding that the method
suggested by the cited references is inherently a method of improving drug
delivery in a patient possessing a functional CYP2D6 gene because “not all
patients possess functional CYP2D6 genes, [and therefore] the allegedly
inherent characteristic does not necessarily flow from the teachings of the
applied prior art” (Appeal Br. 7) and “inherency under § 103 still requires
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that the inherency be known and appreciated in the prior art prior to the time
of the invention” (Reply Br. 2-3).
The issue presented is: Does the evidence of record support the
Examiner’s conclusion that the cited references suggest a “method of
improving drug delivery in a patient possessing a functional CYP2D6 gene,”
as recited in claim 1?
Findings of Fact
1. The Specification discloses that active agents that are metabolized
by CYP2D6 “include risperidone, aripiprazole, … clozapine,” etc. (Spec.
2: 29 to 3: 5).
2. The Specification discloses that CYP2D6 inhibitors include
fluoxetine (id. at 6: 28 to 7: 3).
3. Bymaster discloses that “some schizophrenics which exhibit
depressive episodes during the course of their illness, or depressed
individuals which also have psychotic episodes, may not find total relief
using only an atypical antipsychotic agent” (Bymaster, col. 1, ll. 30-35).
4. Bymaster discloses
a method for treating a patient suffering from or susceptible to
psychosis, acute mania, mild anxiety states, or depression in
combination with psychotic episodes, comprising administering
to said patient an effective amount of a first component which
is an atypical antipsychotic, in combination with an effective
amount of a second component which is a serotonin reuptake
inhibitor.
(Id. at col. 1, ll. 39-45.)
5. Bymaster discloses that atypical antipsychotic agents used to treat
schizophrenia are characterized by “less acute extrapyramidal symptoms”
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(id. at col. 1, ll. 62-65) and include clozapine and risperidone (id. at col. 2,
ll. 16-22).
6. Bymaster discloses that serotonin reuptake inhibitors include
fluoxetine (id. at col. 2, ll. 63-65).
7. Bymaster discloses that “oral administration is not the only route
or even the only preferred route. For example, transdermal administration
may be very desirable for patients who are forgetful or petulant about taking
oral medicine” (id. at col. 9, ll. 33-42).
8. Oshiro discloses carbostyril derivatives that are useful in treating
schizophrenia (Oshiro, col. 1, ll. 5-11) and have reduced side effects,
including “so-called extrapyramidal tract syndromes” (id. at col. 1, ll. 55-
67).
9. Oshiro discloses that its carbostyril derivatives include aripiprazole
(Oshiro, col. 20, ll. 4-7; STN, page 1).
10. Ramstack discloses “microparticles comprising a biodegradable
polymeric binder and a biologically active agent” (Ramstack, abstract).
11. Ramstack discloses that the particles provide “an injectable
system that prevents the loss of dose during treatment, the ability to mix
microparticles containing different drugs, … and the ability to program
release (multiphasic release patterns) to give faster or slower rates of drug
release as needed” (id. at col. 5, ll. 40-46).
12. Ramstack discloses that its system provides “durations of action
ranging from 30 to more than 200 days” (id. at col. 5, ll. 48-51).
13. Ramstack discloses that active agents that can be incorporated in
the microparticles include “psychotherapeutic agents; risperidone … [and]
clozapine” (id. at col. 14, ll. 25-27).
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14. Vandel discloses that “among Caucasians, a lack of cytochrome
enzyme CYP2D6 is observed in 5-10% of individuals” (Vandel, abstract).
Analysis
Claim 1 is directed to a method comprising injecting or implanting an
active agent that is metabolized by CYP2D6, such as aripiprazole (FF 1),
together with an agent that inhibits CYP2D6, such as fluoxetine (FF 2), in an
extended release formulation that releases the active agents for at least about
7 days. Claim 1 also requires performing the claimed method on a patient
possessing a functional CYP2D6 gene.
Bymaster discloses a method of treating a patient suffering from
psychosis and depression by administering an atypical antipsychotic agent,
such as risperidone or clozapine, and a serotonin reuptake inhibitor, such as
fluoxetine. Bymaster also discloses that the drug combination can be
administered transdermally; i.e., by extended release over time. Oshiro (as
evidenced by STN) discloses that aripiprazole is useful for treating
schizophrenia with reduced side effects. Based on these teachings, it would
have been obvious to substitute Oshiro’s aripiprazole for the antipsychotic
agent in Bymaster’s drug combination.
Ramstack discloses injectable microparticles that are formulated with
a polymer and active agent to allow for the extended release (i.e., for 30 or
more days) of the active agent. Ramstack discloses that suitable active
agents include psychotherapeutic agents in general, and risperidone or
clozapine specifically. In view of these disclosures, it would have been
obvious to one of ordinary skill in the art to formulate Bymaster’s
combination of psychotherapeutic agents into Ramstack’s extended release
particles because Ramstack suggests using its particles to administer
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psychotherapeutic agents and Bymaster discloses that an extended release
mode of administration can be beneficial for certain patients. Vandel
discloses that 90-95% of Caucasians, at least, possess a functional CYP2D6
gene; thus, applying the method made obvious by Bymaster and Ramstack
would inherently treat patients possessing a functional CYP2D6 gene.
Appellant argues that the method suggested by the cited references is
not inherently a method of improving drug delivery in a patient possessing a
functional CYP2D6 gene because “not all patients possess functional
CYP2D6 genes, [and therefore] the allegedly inherent characteristic does not
necessarily flow from the teachings of the applied prior art” (Appeal Br. 7).
This argument is not persuasive. Vandel discloses that 90-95% of
Caucasian patients possess a functional CYP2D6 gene. Thus, the treatment
of psychotic patients that is made obvious by the cited references would
result in treatment of a patient “possessing a functional CYP2D6 gene,” as
required by claim 1, at least 9 out of every 10 times it was carried out on a
Caucasian patient. The disputed limitation is therefore met inherently by the
method made obvious by the prior art. See In re Oelrich, 666 F.2d 578, 581
(CCPA 1981) (“If . . . the disclosure is sufficient to show that the natural
result flowing from the operation as taught would result in the performance
of the questioned function, it seems to be well settled that the disclosure
should be regarded as sufficient.”).
Appellant contends, however, that “inherency under § 103 still
requires that the inherency be known and appreciated in the prior art prior to
the time of the invention” (Reply Br. 3-4; citing In re Shetty, 566 F.2d 81
(CCPA 1977)).
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This argument is not persuasive. The cited art suggests an extended
release method of improving drug delivery of antipsychotic agents
(including specific agents that are metabolized by CYP2D6) in psychotic
patients, and the evidence shows that at least the vast majority of Caucasian
patients treated would possess a functional CYP2D6 gene. Thus, the
Examiner’s conclusion of obviousness is not predicated on a theory of
inherency, as was the case in In re Shetty, see 566 F.2d at 86; the Examiner
merely relies on the inherent properties of the method suggested by the prior
art.
Finally, Appellants argue that the Examiner has not shown that the
method made obvious by the cited references “would result in improved
drug delivery for the claimed patient population and not just the
subpopulation of schizophrenic patients receiving aripiprazole who possess a
functional CYP2D6 gene” (Appeal Br. 8).
This argument is also unpersuasive. The Examiner has established
that it would have been obvious to treat at least some patients within the
“claimed patient population;” specifically, Caucasian patients with
schizophrenia. No more is required to show that the claimed method is
unpatentable under 35 U.S.C. § 103(a). See KSR Int’l Co. v. Teleflex Inc.,
550 U.S. 398, 419 (2007) (“If the claim extends to what is obvious, it is
invalid under § 103.”).
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that the
cited references suggest a “method of improving drug delivery in a patient
possessing a functional CYP2D6 gene,” as recited in claim 1.
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SUMMARY
We affirm the rejection of claims 1-7, 10-11 and 13-20 under 35
U.S.C. § 103(a).
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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