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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/23/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Status of the Claims
Claims 1, 20-26, and 31-39 are pending in this application. Claims 2-19 and 27-30 have been cancelled by applicant.
Claim Objections
Claims 34-38 are objected to because of the following informalities:
Claims 34-38 recite “wherein the treprostinil is at about x µg/ about x to about y µg treprostinil.” – wherein x and y are the claimed amounts.
Claims should read “wherein the treprostinil is added in an amount of about x µg/ about x to about y µg.” Or “wherein the treprostinil is present in an amount of about x µg/ about x to about y µg.” Or something to that effect.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 31-33 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 31-33 are indefinite because they read: “wherein the treprostinil is at about 20%/ 0.25 wt% to about 10 wt%/ 1 wt% to about 5 wt% treprostinil.” It is unclear what applicant intends by this. Is the Treprostinil added in an amount so as to make up 20%/ 0.25 wt% to about 10 wt%/ 1 wt% to about 5 wt% of the composition? Or is the Treprostinil added as a solution/ suspension/ mixture comprising 20%/ 0.25 wt% to about 10 wt%/ 1 wt% to about 5 wt% Treprostinil?
Claim Rejections - 35 USC § 103
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.
Claims 1, 20-26, and 31-39 are rejected under 35 U.S.C. 103 as being unpatentable over Guarneri et al. (US 20190321290 – cited in IDS – previously cited) (“Guarneri”); in view of Stenzler et al. (US 20160198758 A1 – cited in IDS – previously cited) (“Stenzler”); and Kelly et al. (WO 2022/072864 – cited in IDS – previously cited) (“Kelly”).
Regarding claim 1, Guarneri teaches a method of making inhalable dry powder composition comprising combining 2,5-diketo-3,6-di-(4-fumaryl-aminobutyl)piperazine (FDKP; instant diketopiperazine compound) and a solution of acetic acid and homogenizing in a high shear mixer to form a precipitate; washing the precipitate in suspension with deionized water; concentrating the suspension and drying the suspension in a spray drying apparatus (Example 1; and para. [0056], [0058]).
FDKP microcrystallites are obtained by preparing a suspension of FDKP (reading on microcrystalline particles consisting essentially of FDKP, as required by the instant claim) 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 (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 (Example 2). Guarneri teaches a composition comprising 2.5-6.25 wt% of FDKP (reading on resuspending the microcrystalline particles forming a resuspension comprising at least 0.2% solid) (Table 1, page 8, col. 1).
Regarding claims 20-21, Guarneri teaches that the FDKP microcrystalline particles have a pore size ranging from about 23.8 nm to 26.2 nm (para. [0072]).
Regarding claims 22-25, Guarneri teaches a composition of aqueous ammonium mixed with 2.5-6.25 wt% of FDKP (reading on resuspension of microcrystallites consisting essentially of FDKP in at least about 0.2% solid) (Table 2, page 8, col. 2).
Regarding claim 26, Guarneri teaches concentrating the suspension and drying the suspension in a spray drying apparatus (para. [0056], [0058]).
Regarding claims 31-33, Guarneri teaches the weight % concentration of treprostinil in the resultant powder was 0.5-10% ([0073] – Example 2) and up to 20 wt% ([0062]).
Regarding claims 34-38, Guarneri teaches doses of their dry powder composition administered comprising 30-180 µg of treprositinil ([0074]) and up to 1-200 µg ([0062]).
Regarding claim 39, Guarneri teaches their microcrystalline particles have surface areas ranging from 59-63 m2/g (Table 2a and [0072]).
Regarding the instantly claimed ranges of: (i) temperature ranging from 13-20 °C (claim 1); (ii) resuspension comprising about 0.2-10% solid (claims 1, 22-25); (iii) pore sizes of 23-30 nm (claims 20-21); (iv) about 0.25-20 wt% treprostinil (claims 31-33); (v) 1-200 µg of treprositinil (claims 34-38); and (vi) 59-63 m2/g surface areas (claim 39); Applicant is advised that Guaneri’s disclosure of: (i) 25°C ± 5°C; (ii) 2.5-6.25 wt% of FDKP; (iii) 23.8 nm to 26.2 nm; (iv) 0.5-20 wt% treprostinil; (v) 1-200 µg of treprositinil; and (vi) surface areas ranging from 59-63 m2/g; respectively, read on the instant claims. The courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. 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); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985) (see MPEP 2144.05.01). The courts have also found that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05-II.
Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
While Guarneri does not specifically teach: (i) pelletizing the suspension consisting essentially of FDKP in a cryogranulator prior to lyophilizing (claim 1); or (ii) resuspension in water and ethanol (claim 1); the teachings of Stenzler and Kelly are relied upon for these disclosures.
Stenzler teaches a method of making nicotine-FDKP microparticle formulations (abstract). It is taught that FDKP microparticles/nicotine suspension can be pelletized (cryogranulated) by flash freezing in liquid nitrogen, and the ice pellets can then by lyophilized, (para. [0046]; claim 12).
Kelly teaches dry powder inhalable composition comprising FDKP and a hydrophobic cannabinoid (abstract; para. [0076], [0102], [0103], and [0166]). 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 (page 25, para. [0079]; claims 1, 2).
Therefore, regarding palletizing the suspension comprising FDKP in a cryogranulator and resuspending in water and ethanol, as recited in claim 1, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention in view of Guarneri in view of Stenzler and Kelly. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because Guarneri discloses their method for making inhalable dry powder composition of FDKP-treprositinil, as disclosed above, wherein the microcrystallites consisting essentially of FDKP (before adding treprositinil) can be washed using deionized water and isolated by lyophilization; further because Stenzler teaches a process wherein similar FDKP microparticles (with nicotine) are pelletized (cryogranulated) prior to being lyophilized. Applicant is advised that a person with ordinary skill has good reason to pursue known options within his or her technical grasp. Note: MPEP 2143(E) KSR, 550 U.S. at 421, 82 USPQ2d at 1397.
Regarding resuspending in water and ethanol, as recited in claim 1, one of ordinary skill would have been motivated to do so with a reasonable expectation of success because Guarneri discloses their microcrystallites comprising essentially of FDKP were re-suspended in an alcohol solution (ethanol) prior to adding the active agent (treprositinil) as a solid or in a suspension or solution; further because Kelly teaches a similar FDKP microparticle formulation wherein FDKP is added to solvent which includes ethanol and water (see [0079]) to obtain FDKP suspension, which is then mixed with their active ingredient. Applicant is reminded that a person with ordinary skill has good reason to pursue known options within his or her technical grasp.
Response to Arguments
Claims
Claim amendments are acknowledged. No new matter has been introduced.
Claim Rejections - 35 USC § 103
Applicant's arguments filed 12/23/2025 have been fully considered but they are not persuasive.
Applicant states Guarneri does not teach or suggest every element of claim 1 and that neither Kelly nor Stenzler cure these deficiencies. Applicant states Kelly does not teach or suggest cryogranulation or any other manipulation of FDKP, nor disclose any preparation or purification method relating to FDKP, and “it would be clear to one of ordinary skill that the “excipient” FDKP of Kelly and the methodically purified FDKP of the present claims are not interchangeable”. Applicant states Stenzler does not teach or suggest cryogranulation of FKDP alone at an intermediate stage, but rather as a final step. Applicant states the office has misinterpreted Stenzler because claim 1 does not use “open ended term when describing FDKP cryogranulation. The suspension of FDKP being pelletized does not include treprostinil or any other ingredient, and that the word “comprising” in the rejection is not accurate as it has been applied to present claim 1”. Applicant further asserts that the office has not presented evidence that the cryogranulation of FDKP is “known” and that Stenzler does not teach or suggest cryogranulation as a method of isolating FDKP. Applicant further argues there is no reason to combine references because the instant treprostinil and Stenzler’s nicotine are not analogous drugs.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
In this case, Guarneri teaches a method of making inhalable dry powder composition comprising FDKP-treprostinil, wherein FDKP microcrystallites are obtained by preparing a suspension of 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 (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 (Example 2).
Stenzler teaches a method of making nicotine-FDKP microparticle formulations (abstract). It is taught that FDKP microparticles/nicotine suspension can be pelletized (cryogranulated) by flash freezing in liquid nitrogen, and the ice pellets can then by lyophilized, (para. [0046]; claim 12).
Kelly teaches dry powder inhalable composition comprising FDKP and a hydrophobic cannabinoid (abstract; para. [0076], [0102], [0103], and [0166]). 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 (page 25, para. [0079]; claims 1, 2).
Therefore, regarding palletizing the suspension comprising PDKP in a cryogranulator and resuspending in water and ethanol, as recited in claim 1, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention in view of Guarneri in view of Stenzler and Kelly. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because Guarneri discloses their method for making inhalable dry powder composition of FDKP-treprositinil, as disclosed above, wherein the microcrystallites consisting essentially of FDKP can be washed using deionized water and isolated by lyophilization; further because Stenzler teaches a process wherein similar FDKP microparticles are pelletized (cryogranulated) prior to being lyophilized.
Regarding resuspending in water and ethanol, as recited in claim 1, one of ordinary skill would have been motivated to do so with a reasonable expectation of success because Guarneri discloses their FDKP microcrystallites were re-suspended in an alcohol solution (ethanol) prior to adding the active agent (treprositinil) as a solid or in a suspension or solution; further because Kelly teaches a similar FDKP microparticle formulation wherein FDKP is added to solvent which includes ethanol and water (see [0079]) to obtain FDKP suspension, which is then mixed with their active ingredient. Applicant is reminded that a person with ordinary skill has good reason to pursue known options within his or her technical grasp.
Regarding Applicant’s argument that Stenzler does not teach or suggest cryogranulation of FKDP alone at an intermediate stage, but rather as a final step; and their assertion that the office has misinterpreted Stenzler because claim 1 does not use “open ended term when describing FDKP cryogranulation; that the suspension of FDKP being pelletized does not include treprostinil or any other ingredient, and that the word “comprising” in the rejection is not accurate as it has been applied to present claim 1”. Applicant is advised that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results (In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930); Ex Parte Rubin, 128 USPQ 440 (Bd. App. 1959)). See MPEP §2144.04 IV C. Therefore, the claimed order of steps is an obvious variant of the steps of the cited prior art; where Guarneri discloses their method for making inhalable dry powder composition of FDKP-treprositinil, as disclosed above, wherein the FDKP microcrystallites can be washed using deionized water and isolated by lyophilization; Stenzler teaches a process wherein similar FDKP microparticles are pelletized (cryogranulated) prior to being lyophilized. Therefore, one of ordinary skill would have been motivated to incorporate Stenzler’s palletization step into Guarneri’s method. Applicant is reminded that a person with ordinary skill has good reason to pursue known options within his or her technical grasp.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JACKSON J HERNANDEZ whose telephone number is (571)272-5382. The examiner can normally be reached Mon - Thurs 7:30 to 5.
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/JACKSON J HERNANDEZ/Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627