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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 27 July 2026 has been entered.
DETAILED OFFICE ACTION
This Office Action is in response to the papers filed on 27 July 2026.
CLAIMS UNDER EXAMINATION
Claims 1-2, 4-14, 16 and 18-23 are pending and have been examined on their merits.
PRIORITY
EP20216444.8, filed on 22 December 2020, is acknowledged. Claim 19 recites the sugar is present in an amount of greater than 0 to less than 5% by weight. Claim 20 has been amended to recite the water-soluble polymer is present in an amount of greater than 0 to less than 5%. Claim 23 recites the sugar or water-soluble polymer is present in an amount of greater than 0 to less than 5%. The Foreign priority document does not provide support for the claimed ranges. Claims 19-20 of PCT/EP2021/087289 provide support for less than 5% of each component.
WITHDRAWN REJECTIONS
The previous rejections have been withdrawn due to claim amendment.
NEW GROUNDS OF REJECTION
New grounds of rejection have been necessitated by claim amendment.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-2, 4-6, 8-9, 11-14, 16, 18 and 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over Burkhardt et al. (Heparin-Based Blood Sampler Without Platelet Activation. WO2019/096598 published 23 May 2019) in view of Ruegg et al. (Treatment of pulmonary hypertension by inhaled iloprost with a microparticle formulation. US20060147520A1) .
Burkhardt teaches a blood sampler (Abstract). A blood sampler is a device for blood collection, including a syringe, capillary tube or test tube (column 18, lines 4-5). The blood sampler comprises at least one anticoagulant and at least one anti-platelet agent (page 4, lines 16-17).
Regarding the anti-platelet agent: The art teaches the anti-platelet agent is a prostaglandin analog, including beraprost, iloprost or treprostinil (page 9, lines 16-20). Iloprost, or a salt thereof, is identified as a preferred antiplatelet agent (page 8, lines 8-10; page 12, lines 6-7). Examiner notes a salt is a solid. Example 1 discloses the use of commercial iloprost which require dissolution. Therefore it is a solid.
Regarding the anticoagulant: Burkhardt teaches the anticoagulant is heparin (page 6, lines 29-31). The art teaches the anticoagulant can be a dry formulation (page 13, line 15). The art teaches a “heparin brick”: at least one anticoagulant in a “puff’ of inert filler material, wherein the puff dissolves and the heparin is dispersed throughout the sample with proper mixing (see page 13, lines 21-30). A dry heparin “brick” is interpreted to be separate from a prostaglandin salt.
Burkhardt does not teach the prostaglandin is in a matrix with water-soluble polymer or sugar.
Ruegg et al. teach an iloprost microparticle formulation (Abstract). The art teaches iloprost is dried in a trehalose (a sugar) glass ([0271] [0533]). Ruegg teaches trehalose is a stabilizing polyol ([0014]).
It would have been obvious to include the prostaglandin taught by Burkhardt in a solid mixture comprising a sugar matrix. Ruegg teaches trehalose is a stabilizer. One would have been motivated to formulate iloprost with trehalose to provide improved stability in the blood sampler. One would have had a reasonable expectation of success since Ruegg teaches trehalose can be combined with a sugar. One would have expected similar results since Burkhardt and Ruegg are both directed to prostaglandins. Therefore claim 1 is rendered obvious.
Burkhardt teaches a syringe, capillary or test tube (supra). Therefore claim 2 is included in this rejection.
Burkhardt does not teach PVP. Ruegg identifies polyvinylpyrrolidone as a matrix ([0073] [0074] [0150] [0151]). Ruegg teaches polyvinylpyrrolidone can be added to a glass matrix to retard recrystallization ([0379] [0426).
It would have been obvious to combine the teachings of the prior art by including the prostaglandin taught by Burkhardt in a mixture with PVP. One would have been motivated to do so to prevent recrystallization. One would have had a reasonable expectation of success since Ruegg teaches iloprost can be added to a glass with iloprost. One would have expected similar results since both references are directed to prostaglandins. Therefore claims 4-6 are included in this rejection.
Burkhardt teaches iloprost. Therefore claims 8-9 are included in this rejection.
Ruegg teaches iloprost is present in an amount from about 0.1% to 20% by weight of the microparticles ([0007]). Claims 11-12 are rendered obvious.
Ruegg teaches a buffer can be incorporated ([0256]). Therefore claim 13 is included in this rejection. Ruegg teaches tromethamine hydrochloride (TRIS) can be included in the microparticles ([0086]). Therefore claim 14 is included in this rejection.
Burkhardt teaches the anticoagulant is electrolyte-balanced heparin (page 7, line 19). Claim 16 is included in this rejection.
The art teaches iloprost is dried in a trehalose (a sugar) glass ([0271]). Ruegg teaches trehalose is a stabilizing polyol ([0014]). Ruegg teaches polyvinylpyrrolidone can be added to a glass matrix to retard recrystallization ([0379] [0426). Therefore claim 18 is rendered obvious.
Regarding independent claim 21:
The teachings of Burkhardt are reiterated.
Burkhardt does not teach the prostaglandin is in a matrix with water-soluble polymer and sugar.
Ruegg et al. teach an iloprost microparticle formulation (Abstract). The art teaches iloprost is dried in a trehalose (a sugar) glass ([0271]). Ruegg teaches trehalose is a stabilizing polyol ([0014]). Ruegg teaches polyvinylpyrrolidone can be added to a glass matrix to retard recrystallization ([0379] [0426).
It would have been obvious to include the iloprost taught by Burkhardt in a solid mixture comprising a sugar matrix. Ruegg teaches trehalose is a stabilizer. One would have been motivated to formulate iloprost with trehalose to provide improved stability. One would have been motivated to include PVP in a glass to prevent recrystallization. One would have had a reasonable expectation of success since Ruegg teaches iloprost can be combined with a trehalose and PVP. One would have expected similar results since Burkhardt and Ruegg are both directed to prostaglandins. Therefore claim 21 is rendered obvious.
Ruegg teaches a glass comprising trehalose. The art teaches the glass can include PVP. Therefore claim 22 is included in this rejection.
Therefore Applicant’s Invention is rendered obvious as claimed.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Burkhardt et al. in view of Ruegg et al. as recited in the rejection of claim 1 above, and further in view of Schillinger et al. (previously cited; Iloprost. New Cardiovasclar Drugs 198: 209-231).
Claim 1 is rejected on the grounds set forth above. The teachings of the prior art are reiterated, Burkhardt teaches iloprost. The art is silent regarding the isomer used.
Schillinger et al. teach iloprost represents a nearly 1:1 mixture of 16(R) and 16(S)-methyl disastereomers which can be resolved by high-performance liquid chromatography or obtained by total synthesis (see page 210, third paragraph).
As an inhibitor of platelet aggregation, the 16S isomer is about five times as potent as the 16R configured isomer (same cited section).
It would have been obvious to use the 16S isomer in the sampler taught by Burkhardt. Burkhardt uses iloprost as an anti-platelet agent One would have been motivated use the 16S isomer since Schillinger teaches the 16S isomer is more potent as an inhibitor of platelet aggregation. One would have had a reasonable expectation of success since Schillinger teaches the 16S isomer can be obtained and Burkardt teaches iloprost can be used in the blood sampler. Therefore claim 10 is included in this rejection.
Therefore Applicant’s Invention is rendered obvious as claimed.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Burkhardt et al. in view of Ruegg et al. as recited in the rejection of claim 1 above, and further in view of Ashland (previously cited; PVP Polyvinylpyrrolidone Polymers. 2014, pages 1-12).
Claim 1 is rejected on the grounds stated above. The teachings of the prior art are reiterated. Ruegg teaches PVP (supra). The art is silent regarding the molecular weight of PVP
Ashland teaches molecular weights are expressed by their K-values, which are based on kinematic viscosity measurements. The K-values assigned to the various grades of PVP represent a function of the average molecular weight, the degree of polymerization and the intrinsic viscosity (see page 3, right column). The art teaches PVP K-15, K-30 and K-60 have molecular weights ranging from 6,000 to 450,000 (see Table II). Viscosity increases with molecule weight (see Table II).
It would have been obvious to use a 6,000 to 450,000 MW PVP to prepare the composition taught by Ruegg. Ruegg teaches PVP, and Ashland teaches viscosity increases with the molecular weight of the PVP species. The skilled artisan would choose a PVP with a molecular weight in the claimed range to optimize the viscosity of the composition. One would have had a reasonable expectation of success since Ruegg teaches PVP can be used to prepare the disclosed composition. One would have expected similar results since both references teach are directed to compositions that contain PVP. Therefore claim 7 is rendered obvious.
Therefore Applicant’s invention is rendered.
Claims 19-20 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Burkhardt et al. in view of Ruegg et al. as recited in the rejection of claim 1 above, and further in view of Palepu et al. (Novel epoprostenol formulation and method of making thereof. 20090088468).
Claims 1 and 21 are rejected on the grounds set forth above. The teachings of the prior are reiterated. Burkhardt teaches a prostacyclin analogs. Ruegg teaches a prostacyclin analog can be formulated with a stabilizing sugar polyol and PVP.
Ruegg teaches the stabilizing polyols is present in a concentration between about 0.1%-about 20% by weight ([0435] [0436]). Ruegg teaches PVP is a matrix material. Ruegg teaches matrix material can be from 5-95% ([0073]).
The art does not explicitly teach sugar can be used in an amount greater than 0 but less than 5%.
The art does not teach PVP can be used in an amount greater than 0 but less than 5%.
Palepu teaches a stable lyophilized epoprostenol composition that can be reconstituted (Abstract). As evidenced by the PG Pub of the instant application, epoprostenol is prostacyclin ([0022]). Palepu teaches a bulking agent ([0039]). Bulking agents include sugars, such as sorbitol, lactose, dextran, maltose, mannose, ribose, sucrose, mannitol, trehalose, lactose, dextran, cyclodextrin; other mono- or polysaccharides; polyvinylpyrrolidine (PVP); or combinations thereof. The bulking agent may be present at 1-5% ([0039]).
It would have been obvious to combine the teachings of the prior art by using less than 5% trehalose. One would have been motivated to do so since Ruegg formulated a prostacyclin analog with a sugar and Palepu teaches prostacyclin can be formulated with 1-5% sugar. One would optimize the amount based on the desired amount of bulking agent in the formulation. One would have had a reasonable expectation of success since Palepu teaches prostacyclin can be formulated with 1-5% sugar. One would have expected similar results since both references are directed to prostacyclin. Therefore claim 19 is rendered obvious.
It would have been obvious to combine the teachings of the prior art by using less than 5% PVP. One would have been motivated to do so since Ruegg formulated a prostacyclin analog with PVP and Palepu teaches prostacyclin can be formulated with 1-5% PVP. One would optimize the amount based on the desired amount of bulking agent in the formulation. One would have had a reasonable expectation of success since Palepu teaches prostacyclin can be formulated with 1-5% PVP. One would have expected similar results since both references are directed to prostacyclin. Therefore claim 20 is rendered obvious.
It would have been obvious to combine the teachings of the prior art by using less than 5% trehalose. One would have been motivated to do so since Ruegg formulated a prostacyclin analog with a sugar and Palepu teaches prostacyclin can be formulated with 1-5% sugar. One would optimize the amount based on the desired amount of bulking agent in the formulation. One would have had a reasonable expectation of success since Palepu teaches prostacyclin can be formulated with 1-5% sugar. One would have expected similar results since both references are directed to prostacyclin. Therefore claim 23 is rendered obvious.
Therefore Applicant’s Invention is rendered obvious as claimed
RESPONSE TO APPLICANT’S ARGUMENTS
The arguments made in the response filed on 27 July 2026 are acknowledged.
Argument : The Applicant argues there is no motivation to combine compositions designed for analyzing blood with compositions designed for therapeutic ingestion or injection. The arguments state claim 1 requires a container 1) configured to collect blood and 2) that is prefilled with the solid mixture prior to blood collection. The Applicant argues Phares, Zhang, Hara, Werk, Schobel and Ashland do not teach this limitation. The Applicant argues the secondary references are directed to administration to the body.
Response: The claims are directed to a device (a blood sampler). Claims 1 and 21 recite a container “configured” to collect blood. The container is pre-filled “prior to collection of the blood such that when collected…” the solid mixture is dissolved. The claims recite the intended use of the container. “Prior to collection” and “such that when collected” are directed to a method of use. The claims recite a solid mixture and heparin salt (both solids).The claim requires the solid mixture and heparin are separate. Therefore blood (a liquid) is not present in the claimed device.
Burkhardt explicitly teaches a blood sampler. The art teaches a container. The art teaches heparin and one of the claimed compounds are in the container. Burkhardt teaches a solid “heparin brick”. This is separate from the prostacyclin salts (solid) disclosed in the art. The deficiency of Burhardt is that it does not teach the prostacyclin is in a mixture comprising a water-soluble polymer and/or a sugar.
Ruegg teaches trehalose (a sugar) stabilizes iloprost. The art teaches iloprost is dried in a trehalose glass. One have been motivated to formulate iloprost with a sugar since Ruegg teaches sugar stabilizes iloprost. Ruegg is not relied upon to teach administration. The reference is relied upon because it teaches formulating iloprost with a sugar to stabilize it. The art also teaches PVP can be used in a glass to control dissolution. Therefore the arguments are not persuasive.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE MOSS whose telephone number is (571) 270-7439. The examiner can normally be reached on Monday-Friday, 8am-5pm EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached on (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is (571) 270-8439.
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/NATALIE M MOSS/ Examiner, Art Unit 1653
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