Ex Parte Richardson et al

Patent Trial and Appeal Board

Dec 14, 2018

13732911 (P.T.A.B. Dec. 14, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
13/732,911 01/02/2013 Peter Richardson
45200 7590 12/18/2018
K&L Gates LLP-Orange County
1 Park Plaza
Twelfth Floor
IRVINE, CA 92614
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
1951300.00251DIV(043) 9277
EXAMINER
LIU, SAMUEL W
ART UNIT PAPER NUMBER
1656
NOTIFICATION DATE DELIVERY MODE
12/18/2018 ELECTRONIC
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.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
uspatentmail@klgates.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte PETER RICHARDSON, ROBERT A. BAUGHMAN,
and DONALD COSTELL0 1
Appeal2017-000783
Application 13/732,911
Technology Center 1600
Before RICHARD M. LEBOVITZ, DAVID COTTA, and TA WEN
CHANG, Administrative Patent Judges.
LEBOVITZ, Administrative Patent Judge.
DECISION ON APPEAL
This appeal involves claims directed to methods for the treatment of
hyperglycemia and/or diabetes in a patient comprising administering GLP-1
and diketopiperazine. The Examiner rejected the claims as anticipated under
35 U.S.C. § 102, as obvious under 35 U.S.C. § 103, and under obviousness-
type double patenting. Pursuant to 35 U.S.C. § 134, Appellants appeal the
Examiner's determination that the claims are unpatentable. We have
jurisdiction under 35 U.S.C. § 6(b). We affirm the Examiner's decision.
1 The Appeal Brief ("Br."; entered Oct. 6, 2015) identifies MannKind
Corporation as the real party in interest (Br. 3).
Appeal2017-000783
Application 13/732,911
STATEMENT OF THE CASE
The Examiner rejected claims 1--4, 6-11, 13, 14, and 16-24 as
follows:
1. Claims 1--4, 6-11, 13, 14 and 16-24 under the judicially created
doctrine of obviousness-type double patenting as being unpatentable over
claims 1-17 of US Pat. No. 8,377,869. Ans. 9.
2. Claims 1-3, 6, 7, 11, 13-16, 18, 19,23, and24underthejudicially
created doctrine of obviousness-type double patenting as being unpatentable
over claims 16, 17, 34 and 35 of Application No. 13/257,284. Ans. 10.
3. Claims 1-3, 6, 7, 11, 13, 14, 16, 18, 19, 23, and 24 under the
judicially created doctrine of obviousness-type double patenting as being
unpatentable over claims 1-3, 7, 8 and 12 of Application No. 13/737,823.
Ans. 10-11.
4. Claims 1-3, 7, 11, 13, 14, 16, 18, 23, and 24 under the judicially
created doctrine of obviousness-type double patenting as being unpatentable
over claims 13-17 of Application No. 14/139,714. Ans. 11. This rejection
is moot because the application was abandoned on Aug. 8, 2016.
5. Claims 1--4, 6-11, 13, 14, and 16-24 under 35 U.S.C. § I03(a) as
obvious in view ofNilsson et al., (US 2006/0120969 Al, published Jun. 8,
2006) ("Nilsson"), Steiner et al., (US Pat. No. 6,652,885 B2, issued Nov. 25,
2003) ("Steiner"), DeFelippis et al., (US 2005/0043228 Al, published Feb.
24, 2005) ("DeFelippis"), Madar et al., (US 2004/0121964 Al, Jun. 24,
2004) ("Madar"), and Caplan et al., (US 2002/0065239 Al, published May
30, 2002) ("Caplan"). Ans. 6. 2
2 The Examiner included claim 15 in the statement of the rejection.
However, claim 15 was canceled. Ans. 3.
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Application 13/732,911
6. Claims 1-4, 6, 7, 11, 13, 14, 16, 18, 19, 23, and 24 under 35 U.S.C.
§ I02(e) as anticipated by Hokenson et al., (US 2008/0260838 Al, published
Oct. 23, 2008) ("Hokenson"). Ans. 4--5.
There are two independent claims on appeal, claims 1 and 13. Claim
1, which is illustrative of the appealed subject matter, reads as follows:
1. A method for the treatment of hyperglycemia and/ or diabetes
in a patient,
comprising the step of administering prandially to said
patient in need of treatment an inhalable dry powder
formulation, comprising a diketopiperazine and a
therapeutically effective amount of a GLP-1 molecule;
wherein said administration does not result in at least one
side effect selected from the group consisting of nausea,
vomiting and profuse sweating.
Br., Claims Appendix, 13.
Claim 13 is similar to claim 1, but is for reducing glucose levels
in Type 2 diabetic patients and the dry powder is administered "pre-
prandially, prandially, peri-prandially, or post-prandially."
OBVIOUSNESS-TYPE DOUBLE PATENTING REJECTIONS
Appellants do not address the obviousness-type double patenting
rejections. Ans. 17. We therefore summarily affirm Rejections 1-3. See
Manual of Patent Examining Procedure§ 1205.02 ("If a ground of rejection
stated by the examiner is not addressed in the appellant's brief, appellant has
waived any challenge to that ground of rejection and the Board may
summarily sustain it."); See also In re Berger, 279 F.3d 975, 984 (Fed. Cir.
2002) (in which the Board affirmed an uncontested rejection of claims under
35 U.S.C. § 112, second paragraph, and on appeal the Federal Circuit
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Application 13/732,911
affirmed the Board's decision and found that the appellant had waived his
right to contest the indefiniteness rejection by not presenting arguments as to
error in the rejection on appeal to the Board).
OBVIOUSNESS REJECTION
The Examiner found that Nilsson describes administering GLP-1
prandially (in connection with a meal) as a dry inhalable powder as required
by claims 1 and 13. Final Act. 4--5. GLP-1 is glucagon-like peptide-I and is
a naturally occurring peptide synthesized in intestinal endocrine cells.
Nilsson ,r,r 2, 6. The Examiner found that Nilsson teaches that GLP-1 is
administered with insulin and can be used to treat diabetes, the same
indication recited in the claims. Final Act. 5. The Examiner stated that
Nilsson does not disclose administering GLP-1 with diketopiperazine
("DKP") as recited in the rejected claims. Id. However, the Examiner found
that DeFelippis teaches DKP is a useful enhancer to increase bioavailability
of GLP-1 when administered as a dry powder by the pulmonary route. Id. 6.
The Examiner further found that Steiner discloses utilizing a species of DKP
in combination with a peptide, such as insulin, to facilitate a rapid increase
of the peptide in the blood, when administered as a dry powder for
pulmonary inhalation. Id. 5.
Based on the teachings in Nilsson, DeFelippis, and Steiner, the
Examiner determined it would have been obvious to one of ordinary skill in
the art to have administered GLP-1 and DKP prandially as a dry powder to
treat diabetes as required by claim 1 for the advantages described in Steiner
"to facilitate transport of active peptide (GLP-1 and insulin) across
biological membrane[ s] resulting in a rapid increase ... of the blood
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Appeal2017-000783
Application 13/732,911
concentration thereof." Final Act. 7. Additionally, the Examiner found that
it would have been obvious to have administered GLP-1 and DKP from the
"teaching [in DeFelippis at ,r 201] that DKP is an 'enhancer' to increase
bioavailability of GLP-1 after pulmonary administration." Id. 7-8.
Appellants contend that the Examiner did not explain why one of
ordinary skill in the art would have found it advantageous to use DKP to
enhance the transport of a peptide across a biological membrane to increase
its blood concentration when Nilsson does not suggest any deficiencies in
pulmonary absorption of its compositions. Br. 10. Rather, Appellants
contend that "Nilsson has already 'solved' the problems associated with
subcutaneous administration through gradually aerosolizing the dose, dulling
any motivation from one of ordinary skill to pursue further 'advantages' in
the composition." Id. 11.
This argument does not persuade us that the Examiner erred. As
discussed by the Examiner, Steiner discloses that DKP is useful for
enhancing the delivery of peptides when administered by pulmonary
inhalation. For example, Steiner teaches:
The diketopiperazines [DKP] also serve both to stabilize and
enhance delivery of the entrapped materials. Formulations also
have been developed for the enhanced transport of active agents
across biological membranes. These formulations include
microparticles formed of (i) the active agent, which may be
charged or neutral, and (ii) a transport enhancer that masks the
charge of the agent and/or that forms hydrogen bonds with the
membrane. The formulations can provide rapid increases in the
concentration of active agent in the blood following
administration of the formulations.
Steiner, col. 4, 11. 11-22.
Steiner also teaches:
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Application 13/732,911
Rapid absorption of a number of other peptides, including
salmon calcitonin, parathyroid hormone 1-34, octreotide,
leuprolide and RSV peptide, has been observed when the
peptide is pulmonarily delivered in fumaryl diketopiperazine-
providing peak blood concentrations within 3-10 minutes after
pulmonary delivery.
Steiner, col. 4, 11. 43--48.
In addition to the teachings in Steiner, Defilippis explicitly teaches
that GLP-1 is less bioavailable when delivered by pulmonary administration
as compared to subcutaneous delivery:
Doses of the compositions of the present invention depend on
the potency and bioavailability of the GLP-1 compound in the
particular composition. Generally, when delivered by the
pulmonary route, the compositions of the present invention will
have a bioavailability that is approximately 10% to 50% that of
the compound delivered subcutaneously. However, an enhancer
such as diketopiperazine may be added to further increase
bioavailability after pulmonary administration.
Defilippis ,r 201.
Thus, while Nilsson may have addressed problems with subcutaneous
delivery by aerosolizing the insulin and GLP-1 for pulmonary delivery
(Nilsson ,r,r 37, 52; Br. 10-11), Defilippis teaches that GLP-1 is less
bioavailable when administered by the pulmonary route as compared to
subcutaneous administration. To address this reduced bioavailability,
Defilippis teaches the addition of DKP when administering GLP-1 by
pulmonary inhalation (Defilippis ,r 201 (reproduced above)), providing an
explicit reason to have used DKP in Nilsson's method of treating diabetes
when delivering GLP-1 by pulmonary inhalation.
Appellants further argue that the "cited prior art" does not teach or
suggest the limitation in claims 1 and 13 of "wherein said administration
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Application 13/732,911
does not result in at least one side effect selected from the group consisting
of nausea, vomiting and profuse sweating." Br. 11-12.
We do not agree. Nilsson teaches:
Advantageously, GLP-1 is inhaled several times daily in
connection with meals, so that the GLP-1 effect on the
pancreatic insulin production is not too small nor leading to too
high concentration in the blood, but so that the GLP-1
concentration is kept within the optimal therapeutic window,
thereby leading to a better control of glucose concentration in
the blood. See FIG. 1, showing two curves, A and B over time
T, representing plasma concentration of GLP-1, where curve A
is the result of a single, high dose administered in the morning
compared to 3 smaller doses administered in direct connection
with meals during the day as in curve B. Curve A shoots over
the permitted maximum level L, which causes unwanted
adverse effects in a subject, such as nausea or inducing
vomiting attacks. Clearly, a better way to achieving glycemic
control is to administer GLP-1 in relatively small doses in
connection with meals.
Nilsson ,r 35 (underlining added).
Thus, Nilsson teaches that when the levels of GLP-1 exceed a
maximum amount, unwanted adverse effects such as nausea and vomiting
occur. Id. However, when it is administered in connection with meals
("relatively small doses in connection with meals") as claimed
("prandially"), such high levels are avoided. Id. Thus, Nilsson reasonably
suggests to one of ordinary skill in the art that prandial delivery of GLP-1
and DPK as claimed could be employed without undue experimentation to
achieve the claimed limitation of claims 1 and 13 in which "said
administration does not result in at least one side effect selected from the
group consisting of nausea, vomiting and profuse sweating."
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Application 13/732,911
Appellants also contend that the cited publications "provide no
expectation of success." Br. 12.
To establish obviousness, there must be a reasonable expectation of
success. In re Merck& Co., Inc., 800 F.2d 1091 (Fed. Cir. 1986). In this
case, Steiner teaches that GLP-1 enhances absorption of peptides when
administered by the pulmonary route (Steiner, col. 4, 11. 43--48) and
DeFelippis that DKP increases GLP-1 bioavailability when provided by the
same route (DeF elippis ,r 201 ). In view of these teachings, Appellants did
not provide objective evidence or scientific reasoning as to why there would
have lack of an expectation of success.
For the foregoing reasons, the obviousness rejection of claims 1 and
13 is affirmed. Dependent claims 2-4, 6-11, 14, and 16-24 fall with claims 1
and 13 because separate reasons for patentability were not provided. See 37
C.F .R. § 41.3 7 ( c )(1 )(iv).
ANTICIPATION BY HOKENSON
Rejection
The Examiner found that Hokenson describes pulmonary
administration of GLP-1 and DKP as a powder to treat diabetes as required
by claims 1 and 13. Final Act. 3. The Examiner found that Hokenson
describes post-prandial administration as recited in claim 13 and prandial
administration as in claim 1. Id. With respect to the requirement of claims
1 and 13 that "said administration does not result in at least one side effect
selected from the group consisting of nausea, vomiting and profuse
sweating," the Examiner did not find that Hokenson expressly teaches that
its GLP-1/DKP composition dry powder formulation avoids the recited side
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Application 13/732,911
effects, but found that, because the composition is identical to the
composition recited in the claims, it would inherently and necessarily
produce the same result as claimed. Id. To support this finding, the
Examiner cited paragraph 99 of the Specification of the Application subject
of this appeal.
Discussion
Inherency ... may not be established by probabilities or
possibilities. The mere fact that a certain thing may result from
a given set of circumstances is not sufficient. (Citations
omitted.) If, however, 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.
In re Oelrich, 666 F.2d 578, 581 (CCPA 1981).
It is well-established that when inherency is the basis of a rejection,
the Examiner must have a "sound basis" for believing that a process carried
out in the prior art produces the same product as claimed. In re Spada, 911
F.2d 705, 708 (Fed. Cir. 1990). Thus, there must be a factual basis that
provides an Examiner with a reason to find that the prior art, while silent,
discloses a product with the same properties as claimed. Once a sound basis
is established, the Examiner can properly shift the burden to applicant to
prove that the prior art process does not produce the same product as
claimed. In re Best, 562 F.2d 1252, 1255 (CCPA 1977).
The Examiner relied upon paragraph 99 of the Specification as
support for the finding that administering GLP-1 and DKP as described in
Hokenson would necessarily result in avoiding the side effects of GLP-1
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Application 13/732,911
administration as recited in the claims. However, paragraph 99 refers to
specific amounts and plasma concentrations of GLP-1 that can be
administered without causing the side effects recited in the claims. 3 In other
words, it appears that some dosages of GLP-1 cause the side effects recited
in claims 1 and 13, but other dosages do not. Paragraph 24 7 of Hokenson is
consistent with this disclosure since Hokenson describes halting a prophetic
"dose" of GLP-1 if the patients experience nausea and/or vomiting,
indicating that the side effects may occur depending on the dosage of GLP-
1. Hokenson ,r 24 7. 4 The Examiner did not provide evidence that the
dosages GLP-1 and DKP utilized to treat diabetes in Hokenson would
necessarily not result in "at least one side effect selected from the group
consisting of nausea, vomiting and profuse sweating" as required to meet the
standard of anticipation when inherency is the basis. Oelrich, 666 F .2d at
3 "In one embodiment, a patient is administered an inhalable GLP-1
formulation in a dosing range wherein the amount of GLP-1 is from about
0.01 mg to about 3 mg, or from about 0.02 mg to about 2.5 mg, or from
about 0.2 mg to about 2 mg of the formulation. In one embodiment, a patient
with type 2 diabetes can be given a GLP-1 dose greater than 3 mg. In this
embodiment, the GLP-1 can be formulated with inhalation particles such as
a diketopiperazines with or without pharmaceutical carriers and excipients.
In one embodiment, pulmonary administration of the GLP-1 formulation can
provide plasma concentrations of GLP-1 greater than 100 pmol/L without
inducing unwanted adverse side effects, such as profuse sweating, nausea
and vomiting to the patient." Spec. ,r 99.
4 "A half-hour dosing lag time will be implemented between subjects in each
cohort to ensure subject safety. The dose may be halted if 3 or more subjects
within a cohort, experience severe nausea and/or vomiting or when the
maximum dose is reached, or at the discretion of the PI [principal
investigator]."
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581. Accordingly, we reverse the anticipation rejection of claims 1 and 13,
and dependent claims 2-4, 6, 7, 11, 14, 16, 18, 19, 23, and 24.
TIME PERIOD
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(l )(iv).
AFFIRMED
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