Atty. Dkt. No. 080618-0716
`Appl. No. 12/591,200
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`Applicant:
`
`Horst OLSCHEWSKI et al.
`
`Title:
`
`TREPROSTINIL ADMINISTRATION BY
`INHALATION
`
`Appl. No.:
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`12/591,200
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`Filing Date:
`
`11/12/2009
`
`Examiner:
`
`Sarah Elizabeth Townsley
`
`Art Unit:
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`1629
`
`Confirmation 4093
`Number:
`
`SUBSTANTNE SUBMISSION UNDER 37 C.F.R. § 1.114
`
`Mail Stop RCE
`Commissioner for Patents
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`Commissioner:
`
`This paper responds to the outstanding Final Office Action dated October 10, 2014,
`
`the Advisory Action dated February 27, 2015 and the Notice of Panel Decision from Pre(cid:173)
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`Appeal Brief Review mailed May 8, 2015, while following the response filed January 12,
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`2015 and the Notice of Appeal filed March 9, 2015. A Request for Continued Examination
`
`including petition for a five month extension of time accompanies this paper.
`
`Amendments to the Claims are reflected in the listing of claims which begins on
`
`page 2 of this document. Remarks begin on page 5 of this document.
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`4822-4063-3381.2
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`Amendments to the Claims:
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`This listing of claims will replace all prior versions, and listings, of claims in the application:
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`Atty. Dkt. No. 080618-0716
`Appl. No. 12/591,200
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`Listing of Claims:
`
`1-17. (Canceled)
`
`18.
`
`(Previously Presented) A method of treating pulmonary hypertension
`
`compnsmg:
`
`administering by inhalation to a human in need thereof a therapeutically effective single
`
`event dose of an inhalable formulation with a pulsed ultrasonic nebulizer, wherein said
`
`therapeutically effective single event dose comprises from 15 µg to 90 µg of treprostinil or a
`
`pharmaceutically acceptable salt thereof, said therapeutically effective single event dose is
`
`inhaled in 18 or less breaths by the human.
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`19.-24. (Canceled)
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`25.
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`(Previously Presented) The method of claim 18, wherein the single event dose
`
`contains from 15 µg to 60 µg of treprostinil or a pharmaceutically acceptable salt thereof.
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`26-27. (Canceled)
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`28.
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`(Previously Presented) The method of claim 18, wherein said administering
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`does not significantly disrupt gas exchange in said human.
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`2 9.
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`(Previously Presented) The method of claim 18, wherein said administering
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`does not significantly affect heart rate of said human.
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`30.
`
`(Previously Presented) The method of claim 18, wherein said administering
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`does not significantly affect systemic arterial pressure and systemic arterial resistance of said
`
`human.
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`31.
`
`(Canceled)
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`32.
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`(Previously Presented) The method of claim 18, wherein said administering of
`
`said therapeutically effective single event dose is performed in 5 or less breaths.
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`33.
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`(Previously Presented) The method of claim 18, wherein said human receives
`
`several therapeutically effective single event doses per day.
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`34.
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`(Previously Presented) The method of claim 27, wherein the concentration of
`
`said treprostinil or a pharmaceutically acceptable salt thereof in the aerosolable solution is
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`600 µg/ml.
`
`35.
`
`(Previously Presented) The method of claim 18, wherein the single event dose
`
`is administered in 5 minutes or less.
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`3 6.
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`(Previously Presented) The method of claim 27, wherein the single event dose
`
`is administered in 5 minutes or less.
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`37.
`
`(Previously Presented) The method of claim 34, wherein the single event dose
`
`is administered in 5 minutes or less.
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`3 8.
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`(Previously Presented) The method of claim 18, wherein said therapeutically
`
`effective single event dose is inhaled in 12 or less breaths by the human.
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`3 9.
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`(Previously Presented) The method of claim 27, wherein said therapeutically
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`effective single event dose is inhaled in 12 or less breaths by the human.
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`40.
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`(Previously Presented) The method of claim 34, wherein said therapeutically
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`effective single event dose is inhaled in 12 or less breaths by the human.
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`41.
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`(New) A method of treating pulmonary hypertension comprising:
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`administering by inhalation to a human in need thereof a therapeutically effective single
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`event dose of an inhalable formulation with a pulsed ultrasonic nebulizer having a
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`concentration of said treprostinil or a pharmaceutically acceptable salt thereof from 500
`
`µg/ml to 2000 µg/ml, wherein said therapeutically effective single event dose comprises from
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`4822-4063-3381.2
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`Appl. No. 12/591,200
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`15 µg to 90 µg of treprostinil, or its acid derivative, or a pharmaceutically acceptable salt
`
`thereof, said therapeutically effective single event dose being inhaled in 18 or less breaths by
`
`the human.
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`42.
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`(New) A method of treating pulmonary hypertension comprising:
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`administering by inhalation to a human in need thereof a therapeutically effective single
`
`event dose of an inhalable formulation with a pulsed ultrasonic nebulizer having a
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`concentration of said treprostinil or a pharmaceutically acceptable salt thereof of 600 µg/ml,
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`wherein said therapeutically effective single event dose comprises from 15 µg to 90 µg of
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`treprostinil, or its acid derivative, or a pharmaceutically acceptable salt thereof, said
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`therapeutically effective single event dose being inhaled in 18 or less breaths by the human.
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`43.
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`(New) The method of claim 18, wherein the pulsed ultrasonic nebulizer
`
`comprises an opto-acoustical trigger for timing inspiration by the human to coincide with
`
`generation of an aerosol pulse produced by the pulsed ultrasonic nebulizer.
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`44.
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`(New) The method of claim 41, wherein the pulsed ultrasonic nebulizer
`
`comprises an opto-acoustical trigger for timing inspiration by the human to coincide with
`
`generation of an aerosol pulse produced by the pulsed ultrasonic nebulizer.
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`45.
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`(New) The method of claim 42, wherein the pulsed ultrasonic nebulizer
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`comprises an opto-acoustical trigger for timing inspiration by the human to coincide with
`
`generation of an aerosol pulse produced by the pulsed ultrasonic nebulizer.
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`46.
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`(New) The method of claim 18, wherein said administering results in
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`pulmonary vasodilation in the human for longer than 3 hours.
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`4822-4063-3381.2
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`Atty. Dkt. No. 080618-0716
`Appl. No. 12/591,200
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`REMARKS
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`Applicants respectfully request reconsideration and allowance of the present
`
`application.
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`CLAIMS STATUS
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`Applicants have added new claims 41-46. Support for the new claims may be found
`
`in throughput the specification as filed including, in examined claims 18 and 27 as well as in
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`paragraph [0094] for claim 41; in examined claim 18 as well as in paragraphs [0070], [0075]
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`and [0078] for claim 42; in paragraph [0078] for claims 43-45; in paragraphs [0093]-[0094]
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`for claim 46. No new matter has been added.
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`Applicants have canceled claim 27, without prejudice or disclaimer.
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`After the amendment, pending claims include a) examined claims 18, 25, 28-30 and
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`32-40 and b) new claims 41-46.
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`CLAIM REJECTIONS UNDER 35 U.S.C. § 103(a)
`
`Claims 18, 25, 27-30 and 32-40 stand rejected as obvious over Chaudry (US
`
`2004/0265238) in view of Cewers (USPN 6,357,671). Applicants respectfully traverse.
`
`The PTO failed to establish a prima facie case of obviousness at least because of the
`
`reasons discussed below.
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`1) The cited references do not teach or suggest the dosage recited in claim 18
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`Chaudry generically encompasses a number of drugs and inhalation devices, creating
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`an enormous number of drug-device dosing possibilities. The only specific guidance
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`provided by Chaudry in relation to treprostinil dosing is found in prophetic example 4,
`
`reproduced here in its entirety:
`
`"Example 4
`[0097]
`5 Treprostinil sodium 0.1-10.0 mg/ml Sodium Chloride 2.0-10.0 mg/ml Sodium
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`Hydroxide q.s. Citric Acid q.s. Water q.s.
`
`[0098] Example 4 is a prophetic example of a formulation comprising the vasodilator
`epoprostenol [sic: treprostinil]. Sodium chloride may be added to the solution to
`adjust tonicity, and sodium hydroxide and citric acid are added to adjust the pH of the
`solution. The solution of Example 4 may be made by methods known to those of
`ordinary skill in the art.
`
`At best, this prophetic example gives a range of treprostinil concentration that varies 100-fold
`
`between 0.1 mg/ml to 10.0 mg/ml. More importantly, however. it fails to give any disclosure
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`of how much treprostinil should be given per inhalation event to a human subject suffering
`
`from pulmonary hypertension, which depends not only on the concentration of the inhaled
`
`solution. the type of nebulizer and the number of breaths. Thus, one of ordinary skill in the
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`art would not have arrived at the method recited in claim 18 based on the cited references.
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`In sum, the PTO failed to establish a prima facie case of obviousness because the
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`cited references do not teach or suggest all the elements of the claimed invention.
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`Accordingly, Applicants request withdrawal of the rejection.
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`2) The cited references do not teach or suggest a pulsed ultrasonic nebulizer
`
`recited in pending claims.
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`The PTO explicitly admits on page 10, lines 5-6, of the Final Office Action that
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`Chaudry does not teach a pulsed ultrasonic nebulizer recited in claim 18. To remedy these
`
`deficiencies of Chaudry, the PTO relies on Cewers. It appears that the PTO mistakenly cites
`
`Cewers based on a key word search that identified certain words being present in the text of
`
`the document, such as "acoustic" and "pulse". In fact, Cewers is far removed from the pulsed
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`ultrasonic nebulizer of the present claims that controls the amount of drug administered per
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`inhalation event, and it does not remotely suggest the use of an "opto-acoustical trigger" as
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`recited in the dependent claims.
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`The specification of the pending application describes the pulsed ultrasonic nebulizer
`
`in paragraph [0070] as "mimicking a metered dose inhaler;" a metered dose inhaler is defined
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`in paragraph [0040] as an inhaler "capable of delivering a metered or bolus dose of a
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`respiratory drug to the lungs." This is achieved by the pulsed ultrasonic nebulizer through a
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`pulse of aerosol production followed by a pause, as described in paragraph [0078] with the
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`exemplary Optineb nebulizer.
`
`Cewers broadly discloses the use of an ultrasonic nebulizer with output control
`
`relative to the amount of drug remaining in the device. Cewers discloses that the liquid level
`
`information obtained during a first and a second measurement period may be compared to
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`determine the amount of liquid nebulized during the intervening nebulization period to
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`provide dose information. Cewers at col. 3, 11. 51-63. The dose information is determined by
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`an emitted acoustic pulse reflected into the chamber that is used in a manner similar to sonar
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`detection to determine the amount of drug remaining in the chamber. Cewers at col. 3 11.1-9
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`and claim 1. Such a pulse is a "feedback" pulse, meaning that a reflected sound wave is used
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`to give the depth of fluid that remains in the nebulization chamber and has no impact on the
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`dose delivered nor does it guide the human subject to time inhalation with the generation of a
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`pulse of aerosol. Cewers at col. 2 11. 56-61. Accordingly, the operation of Cewers is
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`completely different from the pulsed ultrasonic nebulizer of the instant claims.
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`Unlike the device disclosed in Cewers, a pulsed ultrasonic nebulizer offers a distinct
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`advantage of reducing waste of the nebulized drug. A pulsed ultrasonic nebulizer generates
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`pulses of aerosol spaced apart in time. The pulses allow inspiration of each pulse, and the
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`pauses in between prevent drug being wasted when inspiration is not occurring. The pauses
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`also reduces the risk that persons will be unintentionally exposed to drug that is not inhaled,
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`"thereby providing exact dosage." See paragraph 7 4 of the present specification.
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`The presently claimed methods use a pulsed ultrasonic nebulizer with a starting
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`solution of treprostinil having a certain drug concentration range. The pauses between pulses
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`of aerosol allows the human to inhale a precise amount of drug that varies between 15 to 90
`
`micrograms in 18 or less breaths. By contrast, Cewers uses acoustical pulses to determine the
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`depth of liquid inside the nebulizer chamber to determine how much drug remains.
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`3) Secondary considerations of unobviousness
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`Any possible case of obviousness is rebutted by the strong evidence of secondary
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`considerations, such as skepticism of others and long felt need, commercial success and
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`4822-4063-3381.2
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`unexpected clinical results, which are set forth in the enclosed declaration under 37 C.F.R. §
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`1.132 by Dr. Roham T. Zamanian.
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`According to Dr. Zamanian, Chaudry teaches treprostinil and iloprost as
`
`interchangeable compounds, Zamanian at ii 9. Dr. Zamanian uses Tyvaso®, which is FDA
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`approved for use with pulmonary hypertension and currently available on the market, as an
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`exemplary embodiment of the claimed invention and compares it to Ventavis®, which is
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`inhalable formulation for treating pulmonary hypertension containing iloprost, which is also
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`FDA approved and currently available on the market, Zamanian at ii10. According to Dr
`
`Zaminian, "[c]ontrary to the disclosure of Chaudry, Tyvaso® is not interchangeable with
`
`Ventavis®; rather, based on his clinical experience and the surrounding literature, Tyvaso®
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`is preferable to Ventavis®," Zamanian at ii 11.
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`According to Dr. Zamanian, there was skepticism of others and long-felt need prior to
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`Tyvaso®. "As of May 15, 2006, the results of the Aerosolized Iloprost Randomized (AIR)
`
`Study documenting the effects of inhaled iloprost had been public about three and a half
`
`years, and Ventavis® had only been on the market for about one and a half years," Zamanian
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`at ii 12. "Clinicians were largely still of the opinion that intravenous administration of a
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`prostacyclin analog was preferable to inhaled delivery. Thus, there was concern that the
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`adoption of Ventavis® could be happening too rapidly without a full understanding of the
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`side effects," Zamanian at ii 13. "Further, adoption ofVentavis® posed a number of issues.
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`For instance, Ventavis® required administration 6-9 times daily, which was considered
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`challenging for patients to implement. Moreover, clinicians remained concerned about the
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`lack of nocturnal dosing and physiologic impact of withdrawal during the night and early
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`morning hours. There were concerns on how to address the interaction between the patient
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`and the nebulizer and how to administer the therapy if the patient was either altered in mental
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`status or intubated in the intensive care unit," Zamanian at ii 14. "As of May 15, 2006,
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`clinicians would not have arrived at a method of treatment using inhaled treprostinil
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`according to the present claims. There was too much uncertainty as to the effects of inhaled
`
`iloprost to speculate the potential effects of another inhaled formulation comprising a
`
`prostacyclin analog. Indeed, the medical community remained convinced that intravenous
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`administration was preferable to inhalable therapeutics," Zamanian at ii 15. "Moreover, at
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`that time, the pharmacodynamics of inhaled treprostinil would have been unpredictable; thus,
`
`precluding the ability to arrive at dosing regimens such as those claimed. Factors such as
`
`half-life, drug-drug interactions, and adverse events could not be predicted based on the then
`available formulations of treprostinil," Zamanian at iJ 16. "For at least these reasons, the
`benefits of inhaled treprostinil - such as those listed in the specification of the pending
`
`application at, for example, paragraphs [0081] to [0088] and in Figures 6, 10, and 11
`
`(discussed in detail below)-would not have been contemplated or expected as of May 15,
`2006," Zamanian at iJ 17.
`According to Dr. Zamanian, Tyvaso® had a commercial success compared to
`
`Ventavis®. "[O]nce Tyvaso® entered the market, it was clinically preferred to Ventavis®.
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`As indicated by the graph below, after its entry onto the market, Tyvaso® rapidly increased
`
`its market share, while the share held by Ventavis® rapidly decreased" as illustrated by the
`graph below, Zamanian at iJ 18.
`
`US ~hatedl ~Hn Market Sh&n
`
`100
`
`. Dr. Zamanian believes
`
`that this tradeoff in market share results from the clinical advantages that Tyvaso® has over
`
`Ventavis®. The clinical advantages ofTyvaso® over Ventavis® result from A) less frequent
`administration of Tyvaso® compared to Ventavis®, Zamanian at iii! 20-24 and B) patient's
`preference of the pulsed ultrasonic nebulizer used with Tyvaso® compared to Ventavis®,
`Zamanian at iii! 25-28.
`As for frequency of administration, Dr. Zamanian explains that "[b ]ecause of the
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`pharmacodynamic differences between iloprost and treprostinil, Tyvaso® does not need to be
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`administered as frequently as Ventavis®, leading to higher patient compliance," Zamanian, at
`ii 20. "Ventavis® (inhaled iloprost) has a half-life between 20-25 min. As a result,
`Ventavis® needs to be used 6-9 times a day, as frequent as every 2 hours," Zamanian at ii 21.
`"In contrast, Tyvaso® (inhaled treprostinil) has a much longer half-life when inhaled by
`
`human subjects suffering from pulmonary hypertension. This allows Tyvaso® to be
`administered markedly less frequently - about 1 to 4 times a day," Zamanian at ii 22. In Dr.
`Zamanian's practice, he has "found that patients are more likely to comply with a regimen
`
`that requires less frequent administrations; thus, Tyvaso® has been preferable,'' Zamanian at
`ii 23. "Furthermore, the fact that Ventavis® has a short half-life results in periods where
`patients may be off-medication while asleep unless they wake up to take a dose of the drug.
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`Nocturnal hypoxemia is a common symptom of patients with pulmonary hypertension; thus,
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`periods where a patient is off-medication and asleep present face less risk if Tyvaso® is
`prescribed instead ofVentavis®," Zamanian at ii 24.
`As for the advantages of the pulsed ultrasonic nebulizer used with Tyvaso® over an
`
`adaptive aerosol delivery (AAD) nebulizer employed with Ventavis®, Dr. Zamanian
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`provides the following explanation. "The differences in the devices used to administer each
`drug also results in higher patient preference and compliance with Tyvaso®," Zamanian at ii
`25. "Ventavis® employs an adaptive aerosol delivery (AAD) nebulizer. See Ventavis®
`
`Patient Brochure (EXHIBIT 5). Such a device adjusts the dose amount to the volume of the
`
`breath the patient takes in. Thus, the duration of use of the device is dependent on the
`
`patient's breathing. This can lead to the time engagement required to deliver the drug
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`ranging from 10-20 min, depending on the AAD device. Each time the patient uses the
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`device, the patient has to load in the drug. Once the dose is delivered, the patient has to take
`
`apart the device, remove the mesh, and then clean the mesh in distilled water. Each use of
`Ventavis® is, thus, a time-intensive process," Zamanian ii at 26. "In contrast, Tyvaso®
`employs a pulsed ultrasonic nebulizer, as indicated in the pending claims. See Tyvaso®
`
`Patient Brochure (EXHIBIT 6). With this device, the dose is a fixed bolus dose per breath;
`
`thus, the dosing is based on breath number, e.g. 18 breaths or less as claimed. Id; see also
`
`Specification at paragraphs [0040], [0070], and [0078]. Unlike the Ventavis® device, this
`
`device is filled once a day; nothing in the way of cleaning or disassembly is done with the
`device until the end of the day." Zamanian at ii 27. According to Dr. Zamanian, in his
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`clinical practice, he has "found that this results in a better patient experience and, thus, higher
`patient compliance," Zamanian at ii 28.
`According to Dr. Zamanian, "aerosolized treprostinil administered according to the
`
`instant claims has a dose dependent and longer pharmacokinetic effect than would be
`
`expected based on iloprost," Zamanian at 29. "As noted in paragraph [0081], while the
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`maximum effect of aerosolized iloprost and treprostinil on pulmonary vascular resistance
`
`(PVR) was comparable, treatment with treprostinil achieved this maximum effect much
`
`sooner and lasted for a longer duration compared to treatment with iloprost. Further, while
`
`iloprost is known to reduce systemic arterial pressure (SAP), Figure 6C demonstrates that
`administration of treprostinil does not result in this same reduction of SAP," Zamanian at ii
`30. "Regardless of pulse number in which dose was administered, administration of
`
`aerosolized treprostinil resulted in no significant effect on SAP. Of particular clinical interest
`
`is the high reduction of PVR achieved in a three-pulse administration of 15 µg of treprostinil,
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`which appears to have the most modest impact on SAP based on Figures 10 and 11,"
`Zamanian at ii 31. "These data suggest that treprostinil is far more pulmonary selective than
`iloprost: a result that would have been unexpected as of May 15, 2006," Zamanian at 32.
`
`Dr. Zamanian concludes his declaration by stating that "[a]lthough not expected as of
`
`May 15, 2006, Tyvaso® is clinically superior to Ventavis® and preferred to Ventavis® for at
`
`least the above mentioned reasons. Further, the claimed method employing inhaled
`
`treprostinil results in unexpected benefits for treatment of pulmonary hypertension,"
`Zamanian at ii 33.
`In sum, Applicants request withdrawal of the rejection in view of evidence of
`
`secondary considerations of non-obviousness provided in Dr. Zamanian's declaration.
`
`4) New claims 41 and 42
`
`New claims 41 and 42 are patentable over the cited references because these claims
`
`include all the elements of claim 18, which is patentable over Chaudry and Cewers for the
`
`reasons discussed above. In addition, claims 41 and 42 are patentable over Chaudry and
`
`Cewers because one of ordinary skill in the art would not have arrived at the particular
`
`treprostinil concentrations recited for use with the pulsed ultrasonic nebulizer of these claims.
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`As noted above, Chaudry's prophetic example 4 teaches a concentration range varying
`
`between 0.1 and 10 mg/ml, but it gives no information about the number of breaths per
`
`dosing event or the type of inhalation device. Nothing in Chau dry or Cewers or the
`
`combination thereof would have led one of ordinary skill in the art to select the type of
`
`device in the present claims, the number of breaths and the particular concentration of claims
`
`41and42.
`
`5) New claim 43-45
`
`New claims 43-45 are patentable over the cited references because they depend on
`
`claims 18, 41 and 42, which are patentable over Chaudry and Cewers for the reasons
`
`discussed above. In addition, claim 43-45 are patentable over the cited prior art because
`
`Chaudry and Cewers do not teach or suggest an opto-acoustical trigger and synchronizing by
`
`the opto-acoustical trigger inspiration by the human with an aerosol pulse generated by the
`
`pulsed ultrasonic nebulizer as each of claim 43-45 recites. Although Cewers mentions a
`
`"trigger" in column 3, lines 28-33, Cewers' trigger is not the opto-acoustical trigger recited in
`
`claims 43-45. Cewers utilizes its trigger to cause oscillations that generate an aerosol cloud -
`
`thus, nebulizing the liquid housed in the disclosed device. Cewers' trigger cannot
`
`synchronize inspiration by the human patient because unlike the opto-acoustical trigger
`
`recited in claims 43-45, Cewers' trigger does not relate in any way to timing of the patient's
`
`inspiration. The opto-acoustical trigger recited in claims 43-45 allows providing exact
`
`dosage by the pulsed ultrasonic nebulizer, see [0078].
`
`6) New claim 46
`
`New claim 46 is patentable over the cited references because it depends on claim 18,
`
`which is patentable over Chaudry and Cewers for the reasons discussed above. In addition,
`
`claim 46 is patentable over the cited prior art because Chaudry and Cewers do not teach that
`
`administering of treprostinil by inhalation as specified in claim 18 pulmonary vasodilation in
`
`the human for longer than 3 hours. Applicants respectfully submit that one of ordinary skill
`
`in the art would not expect such results based on the cited references.
`
`4822-4063-3381.2
`
`-12-
`
`WATSON LABORATORIES, INC. , IPR2017-01622, Ex. 1162, p. 12 of 39
`
`

`

`Atty. Dkt. No. 080618-0716
`Appl. No. 12/591,200
`
`DOUBLE PATENTING REJECTION
`
`Claims 18, 25, 27-30 and 32-34 stand provisionally rejected on the ground of non(cid:173)
`
`statutory obviousness-type double patenting over claims 1, 4-17 and 52-59 of co-pending
`
`Application No. 11/748,205 in view of Chaudry et al. (US Pub. No. 2004/0265328), Byron
`
`(Proc. Am. Thor. Soc. (1), pp. 321-328, 2004) and Cloutier et al. (USPN 6,521,212). This
`
`rejection should be withdrawn in view of abandonment of US Application No. 11/748,205.
`
`CONCLUSION
`
`Applicants believe that the present application is in condition for allowance.
`
`Favorable reconsideration of the application is respectfully requested. The Examiner is
`
`invited to contact the undersigned by telephone if it is felt that a telephone interview would
`
`advance the prosecution of the present application.
`
`The Commissioner is hereby authorized to charge any additional fees which may be
`
`required regarding this application under 3 7 C.F .R. § § 1.16-1.17, or credit any overpayment,
`
`to Deposit Account No. 19-07 41. Should no proper payment be enclosed herewith, as by a
`
`check being in the wrong amount, unsigned, post-dated, otherwise improper or informal or
`
`even entirely missing or a credit card payment form being unsigned, providing incorrect
`
`information resulting in a rejected credit card transaction, or even entirely missing, the
`
`Commissioner is authorized to charge the unpaid amount to Deposit Account No. 19-07 41.
`
`If any extensions of time are needed for timely acceptance of papers submitted herewith,
`
`Applicants hereby petition for such extension under 3 7 C.F .R. § 1.13 6 and authorize payment
`
`of any such extensions fees to Deposit Account No. 19-07 41.
`
`Respectfully submitted,
`
`Date: November 9. 2015
`
`By /Stephen B. Maebius/
`
`FOLEY & LARDNER LLP
`Customer Number: 22428
`Telephone:
`(202) 672-5569
`Facsimile:
`(202) 672-5399
`
`Stephen B. Maebius
`Attorney for Applicants
`Registration No. 35,264
`
`4822-4063-3381.2
`
`-13-
`
`WATSON LABORATORIES, INC. , IPR2017-01622, Ex. 1162, p. 13 of 39
`
`

`

`Atty. Dkt. No. 080618-0716
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`First Inventor Name:
`
`Horst OLSCHEWSKI
`
`Title:
`
`TREPROSTINIL ADMINISTRATION BY
`INHALATION (as amended)
`
`Appl. No.:
`
`12/591,200
`
`Filing Date:
`
`11112/2009
`
`Examiner:
`
`Sara Elizabeth TOWNSLEY
`
`Art Unit:
`
`1629
`
`Confirmation Number: 4093
`
`INFORMATION DISCLOSURE STATEMENT
`UNDER 37 CFR §1.56
`
`Mail Stop RCE
`Commissioner for Patents
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`Commissioner:
`
`Applicant submits herewith documents for the Examiner's consideration in accordance
`
`with 37 CFR §§ 1.56, 1.97 and 1.98.
`
`Applicants respectfully request that each listed document be considered by the Examiner
`
`and be made of record in the present application and that an initialed copy of Form PTO/SB/08
`
`be returned in accordance with MPEP §609.
`
`The submission of any document herewith is not an admission that such document
`
`constitutes prior art against the claims of the present application or that such document is
`
`considered material to patentability as defined in 3 7 CFR § l.56(b ). Applicants do not waive any
`
`4834-3900-8810.1
`
`-1-
`
`WATSON LABORATORIES, INC. , IPR2017-01622, Ex. 1162, p. 14 of 39
`
`

`

`Atty. Dkt. No. 080618-0716
`
`rights to take any action which would be appropriate to antedate or otherwise remove as a
`
`competent reference any document submitted herewith.
`
`TIMING OF THE DISCLOSURE
`
`The listed documents are being submitted in compliance with 37 CFR § l.97(b), before
`
`the mailing of a first Office action after the filing of a RCE.
`
`Although Applicant believes that no fee is required, the Commissioner is hereby
`
`authorized to charge any additional fees which may be due to Deposit Account No. 19-0741.
`
`Respectfully submitted,
`
`Date November 9, 2015
`
`By /Stephen B. Maebius/
`
`FOLEY & LARDNER LLP
`Customer Number: 22428
`Telephone:
`(202) 672-5569
`(202) 672-5399
`Facsimile:
`
`Stephen B. Maebius
`Attorney for Applicant
`Registration No. 35,264
`
`4834-3900-8810.1
`
`-2-
`
`WATSON LABORATORIES, INC. , IPR2017-01622, Ex. 1162, p. 15 of 39
`
`

`

`f"
`
`Substitute for form 1449/PTO
`INFORMATION DISCLOSURE
`STATEMENT BY APPLICANT
`
`Date Submitted: November 9, 2015
`
`"'-Sheet
`
`(use as manv sheets as necessary)
`I ot 13
`I 1
`
`Application Number
`Filini:i Date
`First Named Inventor
`Art Unit
`Examiner Name
`Attorney Docket Number
`
`U.S. PATENT DOCUMENTS
`
`Complete if Known
`12/591,200
`11 /12/2009
`Horst OLSCHEWSKI
`1629
`Sara Elizabeth TOWNSLEY
`080618-0716
`
`~
`
`PTO/SB/08 (modified)
`"I
`
`~--~----,----~--~--~--~-
`
`~xa~i~er
`5
`rntia
`
`I
`
`1
`
`UNPUBLISHED U.S. PATENT APPLICATION DOCUMENTS
`.
`Name of Patentee or Applicant of I
`U.S. Patent Application
`·
`f
`~1t~ _____ Q~cum~L-~~~
`Cited Document
`0
`I Serial Number-Kind Code2
`·
`
`Filing Date of
`Cited Document
`MM-DD-YYYY
`
`Pages, Columns, Lines,
`Where Relevant
`Passages or Relevant
`
`I
`I
`i
`
`Examiner I
`Signature I
`4829-8947-7155.1
`
`Date
`Considered
`
`WATSON LABORATORIES, INC. , IPR2017-01622, Ex. 1162, p. 16 of 39
`
`

`

`r
`
`Substitute for form 1449/PTO
`INFORMATION DISCLOSURE
`STATEMENT BY APPLICANT
`
`Date Submitted: November 9, 2015
`
`(use as manv sheets as necessarv)
`I of 13
`-.,.Sheet 12
`
`---------------:------------r----~-~-------~-~~----------~--~~--- !
`-1
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`·
`_____ ore,igri...f:Jaten~_QIJ.c:JJl'11e2t _1
`Examiner 1· Cite
`No. 1 r Country Code Number
`I
`Initials*
`Kind Code5 (if known)
`
`1
`
`PTO/SB/08 lmodifiedl
`
`Application Number
`Filing Date
`First Named Inventor
`Art Unit
`Examiner Name
`Attorney Docket Number
`
`Complete if Known
`12/591,200
`11 /12/2009
`Horst OLSCHEWSKI
`1629
`Sara Elizabeth TOWNSLEY
`080618-0716
`
`"
`
`....
`
`FOREIGN PATENT DOCUMENTS
`I
`
`Publication Date
`MM-DD-YYYY
`
`Name of Patentee or
`Applicant of Cited Documents
`
`----~----------------~-·------,-----
`
`Pages, Columns, Lines, I
`i
`Where Relevant
`Passages or Relevant I
`
`Fiqures Appear
`
`T6
`
`'
`Examiner Cite
`i No.1
`Initials*
`
`I F48
`
`NON PATENT LITERATURE DOCUMENTS
`Include name of the author (in CAPITAL LETIERS), title of the article (when appropriate), title of the
`item (book, magazine, journal, serial, symposium, catalog, etc.) date, page(s), volume-issue
`number(s), publisher, city and/or country where published.
`
`Agnew JE, Bateman RM, Pavia D, Clarke SW. (1984) Radionuclide demonstration of ventilatory
`[ abnormalities in mild asthma. Clinical Science; 66: 525-531.
`
`-----
`
`1
`
`' Annals of the International Commission on Radiological Protection (ICRP) Vol 28, No. 3, 1998,
`Publication 80, Radiation Dose to Patients from Radiopharmaceuticals.
`
`f-
`
`F50
`
`I
`
`F51
`
`1-------
`
`Blanchard, J.D., Cipolla, D., Liu, K., Morishige, R., Mudumba, S., Thipphawong, J., Taylor, G., Warren,
`S., Radhakrishnan, R., Van Vlasselaer, R., Visor, G. and Starko, K. (2003) Lung Deposition of
`Interferon Gamma-1b following Inhalation via AERx® System vs. Respirgard II™ Nebulizer Proc. ATS
`I Annual Meeting (Abstract A373), Seattle.
`
`Boyd, B., No