Ex Parte Mullen et al

Patent Trial and Appeal Board

Dec 11, 2017

13582940 (P.T.A.B. Dec. 11, 2017)

United States Patent and Trademark Office
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
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Alexandria, Virginia 22313-1450
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APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
13/582,940 10/02/2012 Alexander Mullen UOS-03-US 7896
50446 7590 12/18/2017
HOXIE & ASSOCIATES LLC
75 MAIN STREET , SUITE 203
MILLBURN, NJ 07041
EXAMINER
KASSA, TIGABU
ART UNIT PAPER NUMBER
1619
NOTIFICATION DATE DELIVERY MODE
12/18/2017 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
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ALEXANDER MULLEN, HOWARD STEVENS, and
SARAH ECCLESTON1
Appeal 2017-003894
Application 13/582,940
Technology Center 1600
Before DEMETRA J. MILLS, ERIC B. GRIMES,
and JOHN E. SCHNEIDER, Administrative Patent Judges.
SCHNEIDER, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a tablet
with both immediate and delayed release of an active agent which have been
rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We reverse.
Time dependent release of drugs utilizes a wide range of
physiochemical and physiomechanical strategies. Spec. 1. Common to all
the strategies is that they are activated by fluids after the tablet has been
1 Appellants identify the Real Party in Interest as the University of
Strathclyde. Appeal Br. 3.
Appeal 2017-003894
Application 13/582,940
ingested by the patient. Id. One disadvantage of the delayed release
formulations is that they are often complex which can add to the cost of the
drug. Id. Another disadvantage is that the release mechanism can fail
leading to incorrect or inappropriate administration of the drug. Id. The
Specification describes a formulation wherein a portion of the drug is
released immediately and the remainder is released after a period of delay.
Id.
Claims 17, 18, 20-25, and 37-41 are on appeal.2 Claim 17 is
illustrative of the rejected claims and reads as follows:
17. A press-coated tablet formulation for an immediate,
followed by a delayed release of an active agent, the tablet
comprising:
(a) a core comprising an active agent together with an
excipient(s); and
(b) a delayed release layer surrounding the core and
comprising a wax and a low substituted hydroxypropyl
cellulose in a ratio of 40:60 to 60:40 w/w; wherein the delayed
release layer substantially delays release of the active agent
within the core for between 3-8 hours after administration of the
tablet to a subject and thereafter a pulsed release of the active
agent from the core occurs, such that at least 70% of the active
agent in the core is released within 5-45 minutes and wherein
the low substituted hydroxypropyl cellulose is micronized with
a mean particle diameter of 20 pm and has a molecular weight
of 115,000 and a hydroxypropyl cellulose content of 8%; and
(c) a top-coating layer comprising a portion of an active
agent together with one or more excipients wherein a
substantially immediate pulsed release of the active agent
occurs following administration to the subject of the tablet.
2 Claims 29, 30, 32, 34, and 36 are also pending in the application but have
been withdrawn from consideration as being drawn to a nonelected
invention. Final Act. 2.
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Appeal 2017-003894
Application 13/582,940
The claims stand rejected under 35 U.S.C. § 103(a) as unpatentable
over Ghimire,3 Ueda,4 Penhasi,5 and Issa.6
DISCUSSION
Issue
The issue with respect to this rejection is whether a preponderance of
the evidence supports the Examiner’s conclusion that the claims would have
been obvious over Ghimire combined with Ueda, Penhasi, and Issa.
The Examiner finds that Ghimire discloses a press coated tablet for
time delayed drug release comprising a rapidly disintegrating core and a
barrier layer comprising glyceryl behenate (“GB”) and low-substituted
hydroxypropylcellulose (“L-HPC”) with a ratio of GB to L-HPC ranging
from 65:35 to 75:25. Final Act. 4. The Examiner finds that Ghimire teaches
a tablet where the ratio of GB to L-HPC is 50:50. Id.
The Examiner finds that Ghimire does not teach a tablet where the
active agent is diclofenac and Ghimire does not teach an immediate release
top-coating. Final Act. 4. The Examiner finds that Penhasi and Ueda teach
the use of diclofenac and that Penhasi teaches the use of an immediate
release top-coating. Id. The Examiner finds that Issa discloses the use of L-
HPC as a disintegrating agent in a delayed release composition and lists LH-
3 Ghimire et al., In-vitro/in-vivo correlation ofpulsatile drug release from
press-coated tablet formulations: A pharamcoscintigraphic study in the
beagle dog, 67 Eur. J. Pharm. And Biopharm. 515 (2007) (“Ghimire”).
4 Ueda et al., US 4,871,549, issued Oct. 3, 1989 (“Ueda”).
5 Penhasi et al., US 6,632,451 B2, issued Oct. 14, 2003 (“Penhasi”).
6 Issa et al., WO 2008/129517 A2, published Oct. 30, 2008 (“Issa”).
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Appeal 2017-003894
Application 13/582,940
32 as one of the L-HPCs that can be used in the composition. Final Act. 6—
7. The Examiner concludes:
It would have been obvious to a person of ordinary skill
in the art at the time the present invention was made to select
diclofenac as the active agent and thus produce the instantly
claimed invention because both Penhasi et al. and Ueda et al.
teach delayed release dosage forms comprising diclofenac as
an active. A person of ordinary skill in the art would have
been motivated to select diclofenac in order to treat pain. A
person of ordinary skill in the art would have had a reasonable
expectation of success since Ghimeri [sic] et al. already teach
press-coated tablets for delayed release of an active.
Moreover, both Penhasi et al. and Ueda et al. also teach
delayed release dosage forms comprising diclofenac. One of
ordinary skill in the art would have been motivated to have an
immediate release top coating in a delayed release coating
pulsatile dosage forms because the delivery system of the
invention which contains immediate release and delayed
release pulse provides many advantages over the sustained
delivery of drugs. First, delivery of a desired agent such as a
drug in pulses allows the body time to readjust between doses.
The readjustment time helps alleviate the build-up of tolerance
(column 18, lines 16-20). It would also have been obvious to
select, e.g. LH-32, low-substituted hydroxypropyl cellulose
because Issa et al. teach that commercially available grades of
low substituted HPC like LH-11, LH-21, LH- 22, LH-B 1,
LH-31 and LH-32 may be used as disingerating [sic] agents to
ensure immediate release of the active once the seal coat is
dissolved. The examiner notes that LH-32 is the same
hydroxypropyl cellulose used in the instant application and,
therefore, has the same properties including the molecular
weight, particle diameter and hydroxypropyl content.
Moreover, routine substitution of one commercially available
low-substituted hydroxypropyl cellulose for another is prima
facie obvious and within the purview of one of ordinary skill
in the art in the absence of evidence to the contrary.
Final Act. 7—8.
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Application 13/582,940
Appellants contend Ghimire, either alone or in combination with the
other references, does not teach a tablet with a delayed release of from 3 to 8
hours. Appeal Br. 8. Appellants also contend that Ghimire does not teach or
suggest the use of the specific L-HPC required by the claims. Appeal Br. 8—
9. Appellants argue that there is no motivation to use a different L-HPC nor
is there an expectation that use of a different L-HPC would affect the time
delay for the release of an active ingredient. Appeal Br. 9.
Appellants argue that Ghimire teaches away from the present
invention. Appeal Br. 10. In support of this argument, Appellants point to
the teaching in Ghimire that it is the presence of the wax which retards the
erosion process. Appeal Br. 10. Appellants argue that this teachings would
have motivated one skilled in the art to increase the amount of wax relative
to the L-HPC rather than use a different L-HPC. Appeal Br. 11.
Appellants contend that the remaining references do not remedy the
deficiencies of Ghimire. Appeal Br. 12—15.
Analysis
Appellants have the better argument. Nothing in the present record
shows why one skilled in the art would expect the substitution of one L-HPC
for another would result in an increase in the delay time in releasing an
active ingredient. We agree with Appellants that the teachings of Ghimire
would lead one skilled in the art to adjust the ratio of L-HPC to wax to
adjust the release time. Appeal Br. 11. Ghimire teaches that it is the
presence of the wax that retards the erosion process. Ghimire 519. In
addition, Ghimire shows that only the tablet with a wax to L-HPC ratio of
75:25 yields a delayed release time of just over two hours. Ghimire 518,
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Application 13/582,940
Fig. 1. Tablets with wax to L-HPC ratios similar to those recited in the
claims exhibited delayed release times of just over one hour, less than the
three to eight hours required by the claims. Id. In this case the Examiner
has not shown that the cited references would have suggested a product
having the properties recited in the claims.
The Examiner points to the teachings of Issa to support the
substitution of the LH-21 HPC of Ghimire for LH-32 used in the present
invention. Ans. 12. We are not persuaded. While Issa teaches that the
various L-HPCs are equivalent when it comes to acting as a disintegrating
agent, as the Examiner notes, one skilled in the art would expect the release
profiles would be the same for the two types of HPC. Id. Thus, one skilled
in the art would expect the use of LH-32, at the ratios recited in the claims,
to result in a composition with a delayed release time of about one hour, not
the three to eight hours recited in the claims. One skilled in the art would
not have had an expectation that using LH-32 in the claimed ratios would
result in a longer delay in release time.
The Examiner argues that the references teach that the time delay can
be affected by either the ratio of wax to HPC or the composition of the HPC.
Ans. 15—17. The Examiner, however, does not cite to any teaching in any of
the references to support this proposition. See id. We have reviewed the
reference and find no support in the cited references or otherwise for the
Examiner’s assertion.
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Application 13/582,940
CONCLUSION
We conclude that a preponderance of the evidence does not support
the Examiner’s conclusion that the claims would have been obvious over
Ghimire combined with Ueda, Penhasi, and Issa.
SUMMARY
We reverse the rejection under 35 U.S.C. § 103(a).
REVERSED
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