Exhibit 1012
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`Coalition For Affordable Drugs XI LLC
`Exhibit 1012
`Coalition For Affordable Drugs XI LLC v Insys Pharma, Inc.
`IPR2015-01799
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`

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`INSl0763P0009lUS
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`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
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`In re Application of:
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`S. George Kottayil
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`Serial No.:
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`13/895,124
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`Filed: May 15, 2013
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`Sublingual Fentanyl Spray
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`Examiner:
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`Robert S Landsman
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`Group Art Unit:
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`1647
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`Confirmation No.:
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`3808
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`AMENDMENT
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`Commissioner for Patents
`P.O. Box 1450
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`Alexandria, VA 22313-1450
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`Madam:
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`Responsive to the Office Action mailed March 21, 2014, please amend the above-
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`identified application as indicated below.
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`If any fees are incurred as a result of the filing of this paper, authorization is given to
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`charge Deposit Account No. 23-0785.
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`Amendment to the Claims begin on page 2 of this paper.
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`Remarks begin on page 4 of this paper.
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`Page 1 of 7
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`

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`Response to Office Action mailed March 21, 2014
`Serial No. 13/895,124
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`Amendment to the Claims
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`1.
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`(Currently amended) A sublingual—fen’eanyl—forrnulation comprising discrete liquid
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`droplets of an effective amount of fentanyl or a fentanyl derivative selected from the group
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`consisting of sufentanil, carfentanil, lofentanil and alfatenil, a free base or a pharmaceutically
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`acceptable salt thereof , in a pharmaceutically acceptable liquid carrier; said
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`droplets having a mean diameter of from at—least about 30 to about 70 1-(-) microns.
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`2.
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`(Withdrawn) A method of treating pain comprising sublingually administering a liquid
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`spray formulation in the form of discrete liquid droplets having a mean diameter of at least about
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`10 microns to a human patient experiencing pain, said liquid spray formulation comprising an
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`effective amount of fentanyl, a free base or a pharmaceutically acceptable salt thereof, or
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`derivative thereof, dispersed in a pharmaceutically acceptable liquid carrier.
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`3.
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`(Withdrawn) A multi-dose device for sublingual administration of a drug comprising:
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`a reservoir containin g a liquid formulation comprising fentanyl, a free base or a
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`pharmaceutically acceptable salt thereof, or derivative thereof in a pharmaceutically
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`acceptable liquid carrier; and
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`the device having an actuator which when actuated delivers a therapeutically effective
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`dose of the liquid formulation in the form of liquid droplets having a mean diameter of at
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`least about 10 microns.
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`4.
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`(Currently amended) A non-propellant sublingual fentanyl formulation Comprising
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`discrete liquid droplets of an effective amount of fentanyl in a pharmaceutically acceptable liquid
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`carrier, wherein the sublingual fentanyl formulation comprises:
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`from about 0.001% to about 15% by weight fentanyl free base;
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`from about 50% to about 60% by weight of ethanol; and
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`from about 0.—1w% fl to about 4-0%—% by weight of propylene glycol;
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`said droplets having a mean diameter of at least about 10 microns.
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`Page 2 of 7
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`

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`Response to Office Action mailed March 21, 2014
`Serial No. 13/895,124
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`5.
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`(New) A non-propellant sublingual fentanyl formulation comprising discrete liquid
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`droplets of an effective amount of fentanyl in a pharrnaceutically acceptable liquid carrier,
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`wherein the sublingual fentanyl formulation consists essentially of:
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`from about 0.001% to about 15% by weight fentanyl free base;
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`from about 50% to about 60% by weight of ethanol; and
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`from about 1% to about 30% by weight of propylene glycol;
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`said droplets having a mean diameter of at least about 10 microns.
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`Page 3 of 7
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`

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`Response to Office Action mailed March 21, 2014
`Serial No. 13/895,124
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`REMARKS
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`Claims 1, 4 and 5 are pending. Claims 1 and 4 are currently amended. Support for the
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`amendment to claim 1 regarding specific fentanyl derivatives can be found in paragraph [0043]
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`of the specification. Support for the amendment to claim 1 regarding droplet diameter can be
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`found in paragraph [0020] of the specification. Support for the amendment to claim 4 can be
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`found in paragraph [0099] of the specification. Claim 5 is new.
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`35 U.S.C. § 112 rejections
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`Claim 1 remains rejected under 35 U.S.C. § 112, first paragraph, for lack of enablement
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`and written description. The Office Action maintains that the specification “does not reasonably
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`provide enablement for sublingual formulations comprising ‘derivatives thereof’ ”. Applicants
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`respectfully traverse this rejection. Amended claim 1
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`is limited only to fentanyl and those
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`derivatives disclosed in paragraph [0043] of the specification (i.e. sufentanil, carfentanil,
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`lofentanil,
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`alfentanil).
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`Each of these analogues possesses
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`the
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`same N-Phenyl-N-(4-
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`piperidinyl)propanamide backbone as fentanyl and differ only slightly in the substituents of that
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`backbone. All of these analogues and their effective amounts are well known in the art. What is
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`not well known in the art are sublingual formulations of fentanyl or these analogues that have
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`discrete liquid droplets having a mean diameter of from about 30 to about 70 microns. This
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`slight variation in the identity of the substituents that are attached to the backbone should have
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`little to no effect on the ability to form these discrete liquid droplets. Thus, taking any of the
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`sublingual fentanyl formulations from the specification, which the Office Action admits are
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`enabling, and replacing an effective amount of fentanyl with an effective amount of one of these
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`analogues would not impose undue experimentation on a person having ordinary skill in the art
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`(“PHOSITA”). Thus, applicants respectfully request withdrawal of this rejection.
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`Claiml is rejected under 35 U.S.C. § 112, second paragraph, for lack of definiteness.
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`The Office Action asserts that the claim is confusing because it
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`is drawn to a fentanyl
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`formulation, however, allows for derivatives which are not fentanyl.
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`Claim 1 has been
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`amended to be drawn to a sublingual
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`formulation.
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`Thus, applicants respectfully request
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`withdrawal of this rejection.
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`Page 4 of 7
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`

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`Response to Office Action mailed March 21, 2014
`Serial No. 13/895,124
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`35 U.S.C. §§102/103 Rejections
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`McCarty
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`Claims 1 and 4 remain rejected under 35 U.S.C. §§ 102(e) as anticipated by or, in the
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`alternative under 103(a) as obvious over McCarty (US 2007/0071806). The Office Action
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`asserts that McCarty teaches sublingual fentanyl formulations which comprise ETOH and PG.
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`The Office Action admits that McCarty does not teach droplet sizes of from about 30 to about 70
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`microns. The Office Action asserts that the burden is on the Applicants to show a novel or
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`unobvious difference between the claimed product and the product of the prior art, citing In re
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`Best, 562 F.2d 1252 (CCPA 1977).
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`Applicants respectfully traverse this rejection. In In re Best, the court found that the later
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`filed application was anticipated and obvious over an earlier patent despite the fact that the
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`application’s claims had an additional element not taught by the earlier patent, namely a cooling
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`rate. The court found that removing the heat source would necessarily lead to the cooling rate
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`claimed and that the applicants failed to show that normal cooling rates were not sufficient for
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`the process described in the application.
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`In re Best, does not apply to the instant application because the situation is not analogous.
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`The additional element claimed in the instant application’s claim 1, namely discrete droplets
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`having a mean diameter of from about 30 to about 70 microns, does not necessarily result from
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`the product taught in McCarty. McCarty teaches that a fentanyl formulation could contain
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`ethanol and propylene glycol. However, McCarty does not teach that these formulations are
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`limited to those that are capable of forming discrete droplets having a mean diameter of from
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`about 30 to about 70 microns. Any fentanyl formulation containing ethanol and propylene
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`glycol will not necessarily result in discrete droplets having a mean diameter of from about 30 to
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`about 70 microns. Additionally, McCarty does not teach the concentration ranges described in
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`claim 4 of the instant application.
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`Furthermore,
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`all of McCarty’s examples
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`teach
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`sublingual/buccal tablets, which as a solid do not contain droplets.
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`The Office Action contends that even if McCarty does not meet the limitations of the
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`instant invention under 10[2], it would still have been obvious at the time of the instant invention
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`to have optimized the conditions to provide a formulation with a rapid/desired onset of action to
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`reduce pain quickly as possible.
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`Page 5 of 7
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`

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`Response to Office Action mailed March 21, 2014
`Serial No. 13/895,124
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`McCarty does not
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`teach or suggest
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`that a formulation comprising fentanyl or its
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`derivatives (sufentanil, carfentanil, lofentanil and alfatenil) of any particular droplet size would
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`be useful for treating pain. Thus, a PHOSITA would not have found it obvious to optimize the
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`conditions taught in McCarty, namely sublingual/buccal tablets, to provide the instantly claimed
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`invention of a sublingual spray comprising fentanyl or its derivatives (sufentanil, carfentanil,
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`lofentanil and alfatenil) with discrete liquid droplets having a mean diameter of from about 30 to
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`about 70 microns. Additionally, McCarty does not make obvious the specific concentrations of
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`ETOH and PG in claims 4 and 5.
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`Ross 2003, Ross 2006 or McCarty in View of W7’llTf[€
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`Claims 1 and 4 are rejected under 35 U.S.C. 103(a) as being unpatentable under either
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`Ross (US 2003/0190290) (“Ross 2003”), Ross (US 2006/0062812) (“Ross 2006”) or McCarty
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`each in view of Whittle. The Office Action asserts that Ross 2003, Ross 2006 and McCarty each
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`teach sublingual fentanyl formulations as claimed. The Office Action further asserts that Whittle
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`teaches pharmaceutical formulations for sublingual use which have a droplet size of 15 to 45
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`microns and the claimed proportions of ETOH/PG.
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`Applicants respectfully traverse this rejection. None of the references in view of Whittle
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`teach a fentanyl or fentanyl derivative (sufentanil, carfentanil, lofentanil, alfentanil) sublingual
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`formulation with a discrete liquid droplet having a mean diameter of from about 30 to about 70
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`microns. Furthermore, Whittle teaches ETOH/PG ratios of 60/40 to 40/60. Instant claim 4 and 5
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`have an ETOH/PG ratio 50/4 to 60/6. Thus, none of the references in view of Whittle would
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`make it obvious to a PHOSITA to vary the formulations disclosed in these references to arrive at
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`the instant claimed formulations. Accordingly, Applicants respectfully request
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`that these
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`rejections be withdrawn.
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`Page 6 of 7
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`

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`Response to Office Action mailed March 21, 2014
`Serial No. 13/895,124
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`SUMMARY
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`None of McCarty, Ross 2003, Ross 2006 or Whittle alone or in combination teaches or
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`makes obvious the formulations of claims 1, 4 or 5. Applicants respectfully submit that the
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`pending claims 1, 4 and 5 are patentable. Accordingly, reconsideration of the rejections and
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`allowance of the application are requested. Should the Examiner have any questions concerning
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`the above, he is respectfully requested to contact the undersigned at the telephone number listed
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`below.
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`Respectfully submitted,
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`Date: April 15, 2014
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`/Steven F. Weinstocld
`Steven F. Weinstock, Registration No. 30,117
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`WOOD, PHILLIPS, KATZ,
`CLARK & MORTIMER
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`500 West Madison Street, Suite 1130
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`Chicago, IL 60662-2511
`Tel: (312) 876-2110
`Fax.: (312) 876-2020
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`Page 7 of 7