FINAL 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 .
Status of Claims
Receipt is acknowledged of claim amendments filed on 20 January 2026.
Claims 1-225 are cancelled.
Claims 226-229, 231-235 and 238-242 have been amended.
Claims 236-237 and 243-259 remains withdrawn from consideration.
Claims 226-235 and 238-242 are examined herein to the extent that the R1 is hexadecyl and the sugar is mannitol, e.g., applicant’s elected species.
Information Disclosure Statement
The information disclosure statement (IDS) filed 01/23/2026 and 04/30/2026 have been considered by the Examiner. A signed and initialed copy of the IDS is included with the instant Office Action.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. Claim 226 contains the transitional language “comprising” for the “dry powder composition”. The transitional term “comprising”, which is synonymous with “including,” “containing,” or “characterized by,” is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004). Claim 226 also recites that the dry powder composition comprises amounts of (a), (b) and (c), “wherein the entirety of (a), (b) and (c) is 100 wt%”, which is interpreted that the 100 wt% is in reference to the combined wt% of (a), (b) and (c) and not the total weight of the dry powder composition. In light of this broadest reasonable interpretation, the “dry powder composition” does not exclude additional, unrecited elements.
Rejections Withdrawn
The rejection of claims 226-242 under 35 U.S.C. 103(a) as being unpatentable over MALININ (US 9,255,064; cited in IDS filed 06/16/2023; patent date of 09 February 2016) in view of ARMER (US 2017/0304276 A1, publication date of 26 October 2017, cited in IDS filed 04/01/2024), is withdrawn in view of the claim amendments filed 20 January 2026.
New Grounds of Rejections
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 226-235 and 238-242 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over MALININ (US 9,255,064; cited in IDS filed 06/16/2023; patent date of 09 February 2016) in view of PAN (CN 1593414 A, date published: 16 March 2005, cited in IDS filed 04/30/2026).
Malinin is primarily directed towards prostacyclin compounds, compositions comprising the same, and methods for treating including pulmonary hypertension (abstract).
Regarding claims 226-229 and 242, Malinin a composition comprising a prostacyclin compound of Formula (I), (II) or (III), or a pharmaceutically acceptable salt thereof, for including pulmonary administration to treat pulmonary hypertension (PH) (column 7, lines 10-11; 7, lines 24-28). Malinin discloses specifically a treprostinil alkyl esters Formula (A):
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209
320
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wherein R2 is including a linear C16 alkyl (e.g., R1 is hexadecyl) (column 51, lines 55-58; column 52, Formula (A); column 53, compound C16-TR). Malinin discloses inhaled C16-TR (e.g., R1 is hexadecyl) at a dose of 0.6-18 µg/kg (e.g. dose for 70 kg person is 42 µg-1,260 µg) was well tolerated with no evidence of body weight and organ weight change after dosing for 14 consecutive days (column 82, lines 49-51).
Malinin does not specifically teach that the composition comprises from about 0.5 wt% to about 5 wt% of the compound of Formula (A) including a linear C16 alkyl (e.g., R1 is hexadecyl), from about 25 wt% to about 61 wt% of leucine, and a balance of mannitol for 100% of the entirety of the compound of Formula (A) including a linear C16 alkyl (e.g., R1 is hexadecyl), the leucine and the mannitol. The deficiencies are made up for by the teachings of Pan.
Malinin does not specifically teach dry powder composition comprises (i) from about 0.5 wt% to about 4 wt% of the treprostinil alkyl esters Formula (A) (e.g., Formula (I)), (ii) from about 29 wt% to about 61 wt% leucine, and (iii) the balance being mannitol, wherein the entirety of (i), (ii) and (iii) is 100 wt%, and wherein the dry powder composition is a spray dry powder composition. Malinin does not specifically teach titrating an initial dose to the patient’s highest tolerated dose. The deficiencies are made up for by the teachings of Pan and Therapeutics.
Pan is primarily directed towards dry powder inhalations (abstract of the English translation).
Regarding claims 226, 230-235 and 238-242, Pan teaches powder for inhalation that is produced by spray drying that has good fluidity and low hygroscopicity of the powder, which has excellent storage stability (second page, last paragraph of the English translation). Pan teaches that the powder composition comprises the active in a wt % amount of 0.1-5%, hydrophobic amino acid in an amount of 10%-70% by weight and soluble carrier in an amount of 25%-89.9% by weight. The amount of 0.1-5% by weight, 10%-70% by weight and 25%-89.9% by weight overlaps the ranges “about 0.5 wt% to about 5 wt%”, “from about 25 wt% to about 61 wt%”, and balance amount of mannitol (e.g., about 34 to about 74.5 wt%) recited in claim 226, respectively. The amount of 0.1-5% by weight overlaps the range “at from about 0.5 wt% to about 2 wt%”, “about 0.5 wt% to about 4 wt%”, “about 2 wt% to about 4 wt%” and “from about 45 wt% to about 61 wt%” recited in claims 230-235 and 242, respectively. Thus, the ranges in claims 226 and 230-235 and 242 are rendered prima facie obvious. See In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). See also MPEP 2144.05. Pan teaches the soluble carrier includes mannitol and the hydrophobic amino acid includes leucine (page 3, second paragraph and fourth paragraph of the English translation, respectively). Pan teaches spray drying a solution that comprises the active, hydrophobic amino acid and the water-soluble carrier (page 4, first and second paragraph of the English translation).
It would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to produce a dry powder for inhalation that is produced by spray drying that comprises a compound having the following formula:
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327
500
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,
wherein R2 is including a linear C16 alkyl (e.g., R1 is hexadecyl), hydrophobic amino acid including leucine and water-soluble carrier including mannitol; wherein the amount of the compound having Formula (A), the leucine and the mannitol are present in amount of 0.1-5% by weight, 10%-70% by weight and 25%-89.9% by weight, respectively; and wherein the dose of the compound having Formula (A) includes from 0.6-18 µg/kg (e.g., doses within 42 µg-1,260 µg (e.g., dose for 70 kg person; .6 µg x 70= 42 µg and 18 µg x 70 = 1,260 µg)). The person of ordinary skill in the art would have been motivated to make those modification in order to obtain powder for inhalation has good fluidity and low hygroscopicity of the powder, which has excellent storage stability by formulating compound having Formula (A) as powder containing the active, leucine and mannitol that is produced by spray drying, as taught by Pan. The person of ordinary skill in the art would have reasonably expected success because Malinin a composition comprising a prostacyclin compound of Formula (I), (II) or (III), or a pharmaceutically acceptable salt thereof, for including pulmonary administration to treat pulmonary hypertension (PH) (column 7, lines 10-11; 7, lines 24-28). Malinin discloses specifically a treprostinil alkyl esters Formula (A):
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209
320
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wherein R2 is including a linear C16 alkyl (e.g., R1 is hexadecyl) (column 51, lines 55-58; column 52, Formula (A); column 53, compound C16-TR). Malinin discloses inhaled C16-TR (e.g., R1 is hexadecyl) at a dose of 0.6-18 µg/kg (e.g. dose for 70 kg person is 42 µg-1,260 µg) was well tolerated with no evidence of body weight and organ weight change after dosing for 14 consecutive days (column 82, lines 49-51). Pan teaches powder for inhalation that is produced by spray drying that has good fluidity and low hygroscopicity of the powder, which has excellent storage stability (second page, last paragraph of the English translation). Pan teaches that the powder composition comprises the active in a wt % amount of 0.1-5%, hydrophobic amino acid in an amount of 10%-70% by weight and soluble carrier in an amount of 25%-89.9% by weight (page 3, third paragraph of the English translation). Pan teaches the soluble carrier includes mannitol and the hydrophobic amino acid includes leucine (page 3, second paragraph and fourth paragraph of the English translation, respectively). Pan teaches spray drying a solution that comprises the active, hydrophobic amino acid and the water-soluble carrier (page 4, first and second paragraph of the English translation).
Thus, the claimed invention as a whole is clearly prima facie obvious over the teachings of the prior art.
Response to Arguments and Declaration
Applicant’s arguments and the declaration will be addressed as they pertain to the new grounds of rejection above.
Applicant’s argument and declaration with respect to claims 226-235 and 238-242 have been considered but are moot because the new grounds of rejection described above, which was necessitated by the claim amendments filed 20 January 2026, relies on a different combination of references (e.g., Malinin in view of Pan) and the arguments are mainly directed towards the previously relied on Armer reference.
Thus, for the reasons of record and for the reasons presented above claims 226-235 and 238-242 are rejected under 35 U.S.C. 103(a).
Conclusion and Correspondence
No claims are allowed.
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN P NGUYEN whose telephone number is (571)270-5877. The examiner can normally be reached Monday-Friday 10am-6pm EST.
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/JOHN P NGUYEN/
Examiner, Art Unit 1619
/BENNETT M CELSA/Primary Examiner, Art Unit 1600
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