DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 2/10/2026 has been entered.
Claims 1, 5, 7, 9-12, 14, 15, 30-35, 37-41 are pending.
Applicant’s remarks filed 2/10/2026 with regard to the outstanding double patenting rejections have been acknowledged. Accordingly, the rejections are maintained.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1, 5, 7, 9-12, 14, 15, 30-35, 37-41 are rejected under 35 U.S.C. 103 as being unpatentable over Guarneri et al. (US 2019/0321290, PTO-892 of record), in view of Leigh et al. (WO 2021211916, PTO-892 of record), in view of Kelly et al. (WO 2022/072864, PTO-892), and further in view of Stenzler et al. (US 20160198758 A1, PTO-892).
Guarneri et al. discloses a method of treating pulmonary arterial hypertension (PAH) comprising administering to a patient in need thereof by oral inhalation using a dry powder inhaler a dry powder composition comprising up to 200 µg Treprostinil or a salt thereof, and one or more pharmaceutically acceptable carrier or excipient. See claims 11-15. Guarneri et al. teaches that Treprostinil was first approved PAH and functional class II to class IV status. See para [0018]. Guarneri et al. discloses that the dry powder composition comprises 1 µg to 180 µg of Treprostinil. See para [0062]; claim 4. Guarneri et al. discloses that the carrier or excipient is fumaryl diketopiperazine and comprises microcrystalline particles comprising crystallites of the diketopiperazine and the treprostinil; and it is taught that the dry powder composition is in substantially crystalline form i.e meets instant claim 5. See claims 14; claims 2-5. Guarneri et al. discloses that the pharmaceutical dry powder composition is provided as single cartridges containing 8 µg, 16 µg, 24 µg, 32 µg, 64 µg or 80 µg micrograms of Treprostinil i.e meets instant claim 1, 10 amounts of 32 µg, 64 µg. See paras [0024], [0036], [0041],[0062], [0063], [0064], [0073]. Guarneri et al. discloses that the patient is administered one or more cartridges of the pharmaceutical dry powder composition per dosing. See paras See paras [0024], [0036], [0041],[0062], [0063], [0064], [0073]. Guarneri et al. teaches that one or more carrier and/or excipient are sodium citrate, sodium chloride, leucine or isoleucine, and trehalose. See claim 13. It is taught that the dry powder inhaler comprises a cartridge consisting of a lid and a container. See claim 17. It is taught that dry powder composition is administered in at least one inhalation in less than 10 seconds. See claim 15. It is taught that phosphodiesterase inhibitors including PDE-5 inhibitors can also be formulated for inhalation alone, or in combination with Treprostinil and can be administered subsequently if administered alone, as a combination therapy (meets claims 32, 33, 37, 38, 39). See paras [0033]-[0034]. A method for treating pulmonary arterial hypertension is provided comprising providing a patient in need of treatment a combination therapy using an inhalable dry powder comprising treprostinil and fumaryl diketopiperazine, and administering separately in combination with orally administered drugs selected from prostacyclin analogues, endothelin receptor antagonists (ERAs), including bosentran, ambrisentran and macitentan, soluble guanine cyclase agonists/stimulators such as riociguat, and PDE-5 inhibitors, including sildenafil, vardenafil and tadalafil (meets instant claims 34, 40). See para [0033].
Guarneri et al. teaches a method of making inhalable dry powder composition comprising combining diketopiperazine such as FDKP; (instant fumaryl diketopiperazine compound) in a solution and a solution of acetic acid and homogenizing in a high shear mixer at high pressures of up to 2,000 psi to form a precipitate; washing the precipitate in suspension with deionized water; concentrating the suspension and drying the suspension in a spray drying apparatus. See paras [0056], [0058].
FDKP microcrystallites are obtained by preparing a suspension of 2,5-diketo-3,6-di-(4-fumaryl-aminobutyl)piperazine (FDKP) in an aqueous ammonia solution and combining an acetic acid solution in a high shear mixture at a temperature of about 25°C ± 5°C (i.e encompass about 20°C); FDKP microcrystallites suspension can optionally be washed using deionized water; FDKP microcrystallites can be optionally be isolated spray drying or lyophilization. It is also taught that after washing in water, the resulting particle suspension is lyophilized to remove water and re-suspended in an alcohol solution including ethanol prior to adding the active agent as a solid or in a suspension or solution. See para [0059]. Preparation of dry powder composition comprising microcrystalline FDKP particles and Treprostinil is obtained by adding a solution of 0.2-1.0 wt % treprostinil in ethyl alcohol to a suspension of FDKP microcrystallites; the mixture was spray dried (meets claim1). See EXAMPLE 2. It is taught that the FDKP microcrystalline particles have a pore size ranging from about 23.8 nm to 26.2 nm (meets instant claim 20). See para [0072].
Leigh et al. discloses a method of treating pulmonary hypertension comprising administering to a patient an effective amount of a composition comprising Treprostinil or a pharmaceutically acceptable salt thereof. See page 1, bottom para; claims. Subjects with pulmonary arterial hypertension (PAH) are administered Treprostinil inhalation powder (TreT), and there was significant improvement in PAH impact scores, and a trend of improvement in PAH scores. See pages 64-70, Example 5; pages 69-70 under CONCLUSIONS; patients with PAH Functional Class I to III were employed in the screening (see page 66, Table 17). It is taught that the single event administering dose may be from 7.5 µg to 100 µg, and the number of single administering events can be 1, 2, …or 6 per day. See page 33. It is taught that the doses of Treprostinil in a dry powder formulation, which is used in a dry powder inhaler provided as single cartridges contain 16, 32, 48, 64 mcg (meets instant claims 6, 7). See page 33, table; page 63, Table 13; Table 16, page 66. Treprostinil inhalation powder (TreT) was administered via a dry powder inhaler. See page 63 Example 4. It is taught that the composition may further comprise a diketopiperazine such as fumaryl diketopiperazine (instant compound). See page 32, para 4. Leigh et al. teaches that the composition therein can comprise excipients such as sodium citrate, sodium chloride, leucine or isoleucine and trehalose. See page 23, paras 2-3.
Guarneri et al. does not specifically teach resuspending the microcrystalline particles of the diketopiperazine in a solution of deionized water and ethanol.
Kelly et al. teaches dry powder inhalable composition comprising fumaryl diketopiperazine (FDKP) and a hydrophobic cannabinoid (see para [0166]). See abstract; paras [0076], [0102], [0103]. It is taught that utilizing the spray-drying approach, cannabinoids are mixed into a solvent such as ethanol, ethanol and water; then mixed with a phospholipid to form cannabinoid/phospholipid solution. FDKP is added to solvent which includes ethanol and water to obtain FDKP suspension. FDKP suspension is added to cannabinoid suspension, mixed; and the resulting suspension is spray dried. See page 25, para [0079]; claims 1, 2.
It would be obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to resuspend the microcrystalline particles of the diketopiperazine in a solution of deionized water and ethanol and add treprostinil (active agent) as a solid with mixing until the dry powder is dissolved; and spary dry the resuspension because 1) Guarneri et al. teaches that after washing in water, the resulting particle suspension is lyophilized to remove water and re-suspended in an alcohol solution including ethanol prior to adding the active agent as a solid or in a suspension or solution, and 2) Kelly et al. teaches FDKP is added to solvent which includes ethanol and water to obtain FDKP suspension.
It would be obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to pelletize the suspension comprising FDKP in a cryogranulor before drying the suspension in a lyophilizer because it is known and Stenzler et al. teaches the process of pelletizing FDKP microparticle suspension in a cryogranulator, and the ice pellets can then by lyophilized.
It would have been obvious to a person of ordinary skill in the art to administer the dry powder composition in a single inhalation per cartridge once or more than once per day as in instant claim 1 because Leigh et al. teaches that the number of single administering events can be 1, 2, …or 6 per day.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to employ the crystalline particles of diketopiperazine such as fumaryl diketopiperazine in the dry powder composition therein comprising Treprostinil and/or salt thereof for treating pulmonary arterial hypertension in a patient because 1) Guarneri et al. discloses a method of treating pulmonary arterial hypertension (PAH) comprising administering to a patient in need thereof by oral inhalation using a dry powder inhaler a dry powder composition comprising treprostinil or a salt thereof, and one or more pharmaceutically acceptable carrier or excipient; Guarneri et al. discloses that the carrier or excipient is fumaryl diketopiperazine and comprises microcrystalline particles comprising crystallites of the diketopiperazine and the Treprostinil; Guarneri et al. teaches that Treprostinil was first approved PAH and functional class II to class IV status; and 2) Leigh et al. discloses a method of treating pulmonary hypertension comprising administering to a patient an effective amount of a composition comprising Treprostinil or a pharmaceutically acceptable salt thereof, and Leigh et al. teaches that the composition may further comprise a diketopiperazine. One of ordinary skill in the would have been motivated to employ the crystalline particles of diketonepiperazine such as fumaryl diketopiperazine in the dry powder composition comprising treprostinil with reasonable expectation of success of obtaining a composition for treating pulmonary hypertension, and administering the composition to a patient suffering from pulmonary arterial hypertension.
It would have been obvious to a person of ordinary skill in the art to administer the dry powder composition twice per day as in instant claims 9, 15 because Leigh et al. teaches that the number of single administering events can be 1, 2, …or 6 per day.
It would have been obvious to a person of ordinary skill in the art to optimize the amounts of microcrystalline particles of FDKP (i.e solid as in instant claims) in ethanol. The optimization of amounts of known agents, is considered well in the competence level of an ordinary skilled artisan in science, involving merely routine skill in the art.
Further, it would have been obvious to a person of ordinary skill in the art to optimize the amount of treprostinil in the dry powder composition as in instant claims 31, 36. The optimization of amounts of known agents, is considered well in the competence level of an ordinary skilled artisan in science, involving merely routine skill in the art.
It has been held that it is within the skill in the art to select optimal parameters, such as amounts of ingredients, in a composition in order to achieve a beneficial effect. See In re Boesch, 205 USPQ 215 (CCPA 1980).
Further, it is pointed out that the optimization of result effect parameters e.g., dosage range, dosing regimens, dosing duration is obvious as being within the skill of the artisan, involving merely routine skill in the art.
Regarding the recitation “the treprostinil reaches a Tmax in blood of the patient in less than about 10 minutes” in the claims 1, 10, the cited prior art renders obvious since the coted prior art suggest the administration of the same product to the same patient population. Accordingly, the said administration will result in Tmax of Treprostinil in less than about 10 minutes, since it is the property or result of the composition.
The examiner notes that the method of how the fumaryl diketopiperazine was prepared does not affect the structure or physical properties of the same compound. Therefore, the teachings of the cited prior art would motivate one of ordinary skill in the art to employ the fumaryl diketopiperazine compound, regardless of how it was made, into the herein claimed Treprostinil composition for treating PAH.
Response to Arguments
Applicant’s arguments filed 2/10/2026 with regard to Stenzier have been considered, but are considered moot as Stenzier no longer cited in the rejection under 35 USC 103a. As discussed above, absent evidence to the contrary, the cited prior art discloses the same compound, regardless how it was made. Therefore, possessing the teachings of the cited prior art, one of ordinary skill in the art would have been motivated to employ the Treprostinil – fumaryl diketopiperazine composition in a method to treat PAH.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAN MING R HUI whose telephone number is (571)272-0626. The examiner can normally be reached Mon - Fri 9:30-5:30.
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/SAN MING R HUI/Primary Examiner, Art Unit 1627
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