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 .
DETAILED OFFICE ACTION
This Office Action is in response to the papers filed on 20 February 2026.
CLAIMS UNDER EXAMINATION
Claims 1-2 and 4-20 are pending and have been examined on their merits.
PRIORITY
EP20216444.8, filed on 22 December 2020, is acknowledged.
WITHDRAWN REJECTIONS
The previous rejections have been withdrawn due to claim amendment.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 § 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 10 and 19-20 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.
Claim 10 has been amended to recite “the iloprost is the (8S, 9S, 11R, 12S, 16S)-isomer of iloprost”. The use of the parentheses makes it unclear whether “8S, 9S, 11R, 12S, 16S” are exemplary, or required. It is unclear what isomer is being claimed. Appropriate correction is required.
Claim 19 has been amended to recite the sugar is present “in a positive amount of less than 5%”. It is unclear what range the Applicant is attempting to claim by stating “a positive amount”. The metes and bounds of the claim are unclear. Appropriate correction is required.
Claim 20 has been amended to recite the water-soluble polymer is present “in a positive amount of less than 5%”. It is unclear what range the Applicant is attempting to claim. The metes and bounds of the claim are unclear. Appropriate correction is required.
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, 8-10, 13, 15-16 and 18-19 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 Hara et al. (Sustained-Release Prostaglandin I Derivative Preparation. EP0947196 17 June 2009) as evidenced by Schillinger et al. (previously cited; Iloprost. New Cardiovasclar Drugs 198: 209-231).
Burkhardt teaches a blood sampler (Abstract). The art teaches a blood sampler means 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). The art teaches the anti-platelet agent can be 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). The art teaches the prostaglandin analog can be a salt (therefore a solid). The anticoagulant can be a dry formulation (page 13, line 15). Therefore the art is interpreted to teach a solid composition.
The deficiency of Burkhardt is the reference does not teach a water-soluble polymer or sugar.
Hara teaches a preparation of prostaglandin I derivatives or a salt thereof ([0001]). The prostaglandin is beraprost, iloprost, cicaprost ([0013]). The art teaches a hydrogel base comprising a polymer (a solid) ([0018]). The art teaches hydroxypropyl cellulose (HPC) as said base ([0018]). The art teaches polyvinylpyrrolidine (PVP) ([0023]). The preparation can comprise vehicles including lactose, saccharide and sucrose (sugars) [0023]). Table 1 discloses formulations comprising beraprost sodium, HPC and lactose (a sugar).
It would have been obvious to combine the teachings of the prior art by adding hydroxypropyl cellulose and a sugar to Burkhardt’s composition. Burkhardt teaches a composition comprising a prostaglandin and Hara teaches adding hydroxypropyl cellulose and a sugar to a prostaglandin to prepare a sustained release composition.
One would have had a reasonable expectation of success since Hara teaches HPC and lactose (a sugar) can be successfully combined. One would have expected similar results since both references are directed to prostaglandin compositions. Therefore claim 1 is rendered obvious.
Burkhardt teaches a syringe, capillary or test tube (supra). Therefore claim 2 is included in this rejection.
Hydroxypropyl cellulose is rendered obvious on the grounds stated above. Therefore claim 4 is included in this rejection.
Burkhardt teaches iloprost. Therefor claims 8-9 are included in this rejection.
As evidenced by Schillinger et al, iloprost represents a nearly 1:1 mixture of 16(R) and 16(S)-methyl disastereomers (see page 210, third paragraph). Therefore the iloprost taught by Burkhardt would contain the 16S isomer. Therefore claim 10 is included in this rejection.
Hara teaches a buffer (supra). Therefore claim 13 is included in this rejection.
Burkhardt teaches the anticoagulant is heparin (page 6, lines 29-31). Therefore claim 15 is included in this rejection. In a preferred embodiment, the anticoagulant is electrolyte-balanced heparin (page 7, line 19). Therefore claim 16 is included in this rejection.
Hara teaches beraprost, a sugar and hydroxypropyl cellulose (see Table 1). Therefore claim 18 is included in this rejection.
Hara teaches said sugar is present in an amount from “about 0%” (hence, a positive amount) to preferably 5% of the composition ([0024]).Therefor claim 19 is rendered obvious
Therefore Applicant’s Invention is rendered obvious as claimed.
Claims 1-2, 4-6, 8-10 and 13-16 are rejected under 35 U.S.C. 103 as being unpatentable over Burkhardt in view of Hoke et al. (Sample collection devices with blood stabilizing agents. US20130209985) as evidenced by Schillinger.
The teachings of Burkhardt as set forth above are reiterated.
The deficiency of Burkhardt is the reference does not teach a water-soluble polymer or sugar.
Hoke et al. teach a device for collecting and stabilizing blood (Abstract). The device contains an anti-coagulant and an antiplatelet agent (Abstract). The art teaches a test tube, capillary rube or syringe as a blood collection device ([0023]).The antiplatelet can be iloprost ([0034]). Polyvinylpyrollidone (PVP) and trehalose (sugar) are taught as stabilization agents ([0057] [0059]).
It would have been obvious to add PVP or a sugar to Burkhardt’s composition. One would have been motivated to do so since Burkhadt teaches a device for blood collection and Hoke teaches these components can be used to stabilize blood. One would have had a reasonable expectation of success since Hoke teaches PVP or trehalose (a sugar) can be successfully combined with iloprost. One would have expected similar results since both references are directed to devices for blood collection. Therefore claim 1 is rendered obvious.
Burkhardt teaches a syringe, capillary or test tube (supra). Therefore claim 2 is included in this rejection.
PVP is rendered obvious on the grounds set forth above. Claims 4-6 are included in this rejection.
Burkhardt teaches iloprost. Therefor claims 8-9 are included in this rejection.
As evidenced by Schillinger et al, iloprost represents a nearly 1:1 mixture of 16(R) and 16(S)-methyl disastereomers (see page 210, third paragraph). Therefore the iloprost taught by Burkhardt would contain the 16S isomer. Therefore claim 10 is included in this rejection.
Burkhardt is silent regarding the use of a buffer in the disclosed blood collection system.
Hoke teaches a buffer is added as a stabilization agent ([0059]). Hoke teaches Tris is added to blood collection tubes ([0087]).
It would have been obvious to use a buffer in the composition taught by Burkhardt. One would have been motivated to do so since Hoke teaches buffers can be added to clog collection devices as stabilization agents. One would have had a reasonable expectation of success since Hoke teaches a buffer can be used in a blood collection device with a prostaglandin as an active ingredient. One would have expected similar results since both references are directed to blood collection systems comprising prostaglandins. Therefore claim 13 is rendered obvious. Hoke teaches a Tris buffer. Therefore claim 14 is included in this rejection.
Burkhardt teaches the anticoagulant is heparin (page 6, lines 29-31). Therefore claim 15 is included in this rejection. In a preferred embodiment, the anticoagulant is electrolyte-balanced heparin (page 7, line 19). Therefore claim 16 is included in this rejection.
Therefore Applicant’s Invention is rendered obvious as claimed.
Claims 1-2, 4-6, 8, 11-13 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Phares et al. (previously cited; Solid forms of treprostinil. US20140275262A1) in view of Werk et al. (Technology, Applications, and Process Challenges of Dual Chamber Systems. Journal of Pharmaceutical Sciences. Volume 105, Issue 1, January 2016, Pages 4-9).
Phares et al. teach solid dosage forms of treprostinil (Abstract; [0074]). Phares teaches a powder is a solid dose ([0074]). Treprostinil can be mixed with sugars including lactose and glucose, mannitol and/or binding agents including poly(vinylpyrrolidine) ([0074]). A powder comprising treprostinil, PVP and/or sugars reads on the claimed solid mixture. The art teaches a “powder” (hence, a solid) can be reconstituted with liquids prior to use for parenteral administration ([0072]). The art teaches packaging in a “dual chamber syringe” ([0073]). The syringe reads on the syringe recited in claim 1.
While Phares teaches water-soluble polymers and sugars to prepare a solid, the art does not do so with sufficient specificity to anticipate the claim.
Phares teaches a powder can be reconstituted with a liquid prior to use. Phares does not explicitly teach adding the unreconstituted solid to the syringe.
Werk teaches a dual chamber syringe contains freeze dried drug (hence, powder) in one chamber, and diluent in a separate chamber (see page 5, right column, second paragraph).
It would have been obvious to prepare a solid formulation of treprostinil comprising PVP and a sugar. The skilled artisan would do so to prepare a powder. One would have had a reasonable expectation of success since Phares teaches a sugar or a water-soluble polymer can be used to make a solid composition comprising treprostinil.
It would have been obvious to add the unreconstituted powder taught by Phares to a dual chamber syringe. Phares teaches adding a powder to a dual chamber syringe and Werk teaches powdered drugs are separated from diluents in a dual chamber syringe. The skilled artisan would add solids and liquids to separate chambers of a dual chamber syringe in order to keep the components separated before use. Because the art teaches a syringe, it is configured to collect blood for analysis as recited in claim 1. Therefore claim 1 is rendered obvious.
Phares teaches a syringe (supra). Therefore claim 2 is included in this rejection.
Phares teaches PVP (supra). PVP reads on claims 4-6.
Treprostinil reads on claim 8.
Phares teaches the total active ingredient comprises from 0.1% to 99.9% by weight of the formulation ([0070]). Therefore claims 11-12 are rendered obvious.
The art teaches the dosage form may also contain buffering agents ([0074]). Therefore claim 13 is included in this rejection.
Phares teaches when preparing a solid dose, the compound can be formulated with a sugar and a filler ([0074]). Therefore the use of a sugar and PVP is rendered obvious Therefore claim 18 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 20 February 2026 are acknowledged.
Argument : The arguments state Phares teaches formulations for parenteral administration. The arguments states this means injection. The arguments state adjuvants used in parenteral formulation include wetting agents, emulsifying agents and dispersing agents. Therefore the Applicant argues the art does not teach a solid formulation in a syringe.
Response: The arguments are directed to an intended use. The claims are directed to a product, and not a method. Phares is directed to “solid forms of Treprostinil” (see Title). [0074] teaches a treprostinil powder (solid) may contain PVP and sugar. At [0072] teaches “powders” can be reconstituted with liquids prior to use as a parenteral. The art teaches powder can be packaged in a syringe. The rejection is based on a syringe comprising Treprostinil and PVP/sugar, prior to reconstitution. While the claim has been amended to recite the designation of the syringe and its configuration for blood analysis, the claims are not directed to a method. The claims are directed to a product comprising a syringe, trepostinil, a water-soluble polymer or a sugar. Phares teaches a powder comprising Treprostinil, PVP and sugar and teaches packaging in a syringe. Because the claimed components are rendered obvious, it would be suitable for blood sampling and analysis as recited in claim 1.
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Phares in view of Werk as recited in the rejection of claim 1 above, and further in view of Schobel et al. (System and method for making personalized individual unit doses containing pharmaceutical actives. US2019388302A1).
Claim 1 is rejected on the grounds set forth above. The teachings of Phares and Werk are reiterated. Phares teaches a water-soluble polymer. The art is silent regarding the amount.
Schobel teaches individual unit doses of an active ingredient (Abstract). The active can be iloprost, beraprost, cicaprost ([0154]) or treprostinil ([0137]). The active is added to a carrier matrix (see claim 29 of Schobel). Polyvinyl pyrrolidone and hydroxypropyl cellulose are control release agent identified as matrices ([0168] [0170]). A control release agent can be present in an amount of about 5-80% ([0176]). Schobel teaches said agents control disintegration of the formulation ([0159]).
It would have been obvious to use less than 5% PVP in Phares. Phares teaches a solid prostaglandin composition comprising PVP and Schobel teaches PVP is a control release agent. One would optimize the PVP range taught by Schobel to achieve the desired rate of disintegration. MPEP 2144.05(I) teaches “a prima facie case of obviousness exists where 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 the same properties. One would have expected similar results since Phares and Schobel are both directed to prostaglandin compositions. Therefore claim 20 is rendered obvious.
Therefore Applicant’s Invention is rendered obvious as claimed.
Claims 1-2, 8, 13, 15 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (previously cited; Treprostinil derivatives and compositions and uses thereof. 26 March 2020 US2020/0095186 A1; with benefit of 16/039566 filed on 19 Jul 2018) in view of Werk.
Zhang teaches compositions comprising treprostinil derivatives ([0099]). Zhang et al. disclose a solid composition the contains treprostinil in admixture with, e.g., a filler (e.g., lactose) ([0102]). Lactose is a sugar. The art teaches a powder ([0102]).
Zhang teaches the compositions can be presented as a kit, wherein the active ingredient, excipients and carriers (e.g., solvents) are provided in two or more separate containers (e.g., ampules, vials, tubes, bottles or syringes) and need to be combined to form the composition to be administered ([0113]).
Zhang teaches a composition that reads on the solid mixture recited in claim 1. Zhang teaches a kit. Zhang teaches the components can be in separate containers prior to use. Zhang teaches a syringe. The art does not explicitly the solid component is separate from any solvents.
Werk teaches a dual chamber syringe contains freeze dried drug (hence a powder) in one chamber, and diluent in a separate chamber (see page 5, right column, second paragraph). The art teaches using dual chamber syringes offer ease for patients and healthcare professions (first paragraph of “Summary” on page 8, right column).
It would have been obvious to add the solid taught by Zhang to a dual chamber syringe. Zhang teaches a kit containing the active ingredient, excipients and solvents in separate containers. Werk teaches powdered drugs (solids) are separated from diluents in a dual chamber syringe. The skilled artisan would add the composition to a dual syringe with dry components in a separate chamber since the art teaches the syringe offers ease for health care professionals. One would have had a reasonable expectation of success since Zhang teaches a kit comprising separate containers and Werk teaches a syringe comprising separate chambers (containers). Because Werk teaches a syringe, it is configured to collect blood for analysis as recited in claim 1.
Zhang teaches a syringe (supra). Therefore claim 2 is included in this rejection.
Treprostinil reads on claim 8.
Zhang teaches the use of a buffering agent, such as sodium citrate ([0100] [0107]). Therefore claim 13 is rendered obvious.
Zhang teaches the treprostinil derivative is used to treat PAH ([0132]). An additional therapeutic agent is administered in combination with the treprostinil derivative to treat PAH. The additional therapeutic agent can be contained in the same composition as the treprostinil derivative or in separate compositions ([0132]). The additional therapeutic agent for the treatment of PAH can be an anticoagulant, including heparin and derivatives thereof (e.g., unfractionated heparin, low molecular weight heparin) ([0136]).
At [0197], Zhang contacts test compound (a treprostinil derivative) with heparinated human plasma.
It would have been obvious to use heparin in the disclosed composition. One would do so when using an anticoagulant to treat PAH. One would have had a reasonable expectation of success since Zhang teaches heparin can be used with a composition containing treprostinil derivative. Therefore claim 15 is rendered obvious.
Zhang teaches heparin can be separate from the composition containing treprostinil derivative (supra). Therefore claim 17 is included in this rejection.
Therefore Applicant’s invention is rendered obvious as claimed.
RESPONSE TO APPLICANT’S ARGUMENTS
The arguments made in the response filed on 20 February 2026 are acknowledged.
Argument : The arguments state Zhang does not teach a solid in a test tube, syringe or capillary.
Response: Zhang et al. disclose a solid composition the contains a treprostinil derivative in admixture with, e.g., a filler (e.g., lactose, a sugar) ([0102]). Therefore the art teaches a solid mixture comprising Treprostinil and starch (a water-soluble polymer) and a sugar (lactose). Zhang teaches a kit wherein the active ingredient and solvents are provided in two or more separate containers, including a syringe, and need to be combined prior to administration ([0113]). Werk teaches a dual chamber syringe. The art teaches dry components are separate from diluent. Therefore the arguments are not persuasive.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Phares in view of Werk 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. Phares 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 Phares. Phares 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 Jain 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.
CONCLUSION
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 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) 273-8300.
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/NATALIE M MOSS/ Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653