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 ACTION
Status of the Claims
Claims 14-15, and 17-32 are pending.
Claims 1-13 and 16 have been canceled.
Claims 19 and 25 have been withdrawn.
Claims included in the prosecution are claims 14-15, 17-18, 20-24 and 26-32.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 09/19/2025 has been entered.
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.
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 35 U.S.C. § 103 (a) are summarized as follows:
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue.
Resolving the level of ordinary skill in the pertinent art.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
1. Claims 14, 15, 17, 18, 20, 21, 23, 28, and 30-32 are rejected under 35 U.S.C. § 103 as being unpatentable over Phares et al. (US 2017/0095432 A1) in view of Macdonald et al. (US 20120245561 A1) with evidence from Wagenaar (Caltech Neurotechnology Laboratory Syringe needle gauge, Table pages 1-2).
Phares teaches a composition comprising a) treprostinil or its derivative and b) an anion ion exchange resin, which is preferably in the form of an ion complex ([0003]). In an embodiment Phares teaches a pharmaceutical formulation comprising such ion complex of treprostinil or its derivative and a pharmaceutically acceptable carrier ([0004]). Treprostinil-ion exchange resin complexes may be used for treating a condition, for which treprostinil is known to be useful, by administering a therapeutically effective amount of a composition comprising a treprostinil-ion exchange ion complex to a subject, such as a human being, in need thereof. Such conditions include pulmonary hypertension ([0044]). The composition comprises a treprostinil-ion exchange ion complex administered to a subject to treat pulmonary arterial hypertension ([0044], claim 19).
Phares teaches that the formulation of the composition is a suspension (claim 11).
Phares teaches that the treprostinil ion-exchange resin complexes may be formulated for delivery by a suitable route by injection including, intraperitoneally, intramuscularly, subcutaneously, intraadiposally, intraarticularly, intravenously, or intrathecally ([0046]).
Phares teaches that the formulation of the composition is a controlled-release formulation providing a controlled release of the tresprostinil over a time period ranging from 1 hour to 36 hours (claim 18) which encompasses a 24-hour period to meet the sustained-release treatment period of at least one day when administered to the patient requirement of the claims. Phares provides specific examples as part of a study performed to develop a sustained-release liquid dosage form of treprostinil, in which the rate of release of the drug (treprostinil) may be controlled ([0064] see EXAMPLE). In the study of Phares, the complex between treprostinil and an ion-exchange resins (IER), namely a cholestyramine resin, was characterized as a candidate for use in a sustained-release dosage form of treprostinil ([0064]). Phares emphasizes that the programmable release rate may be controlled principally by at least one of two variables—(1) the thickness of the polymer coating and (2) the use of a release retardant component added to the treprostinil-ion exchange resin complex to form a fine particulate matrix prior to the polymer film coating step ([0043], claim 17). In light of this study and these teachings of a release being controlled by the aforementioned two variables, particle size would be readily optimized by a person of skill in the art. MPEP 2144.05 states 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.
Regarding the step of injection comprising passing the liquid dispersion through a needle of an injection device while the liquid dispersion is in contact with the needle until the passing of the liquid dispersion through the needle ceases, Phares does not provide such step.
However, MacDonald discloses a method that provides a flowable sustained release microparticulate composition comprising: (i) a microparticulate formulation comprising at least one therapeutic agent, and (ii) a pharmaceutically acceptable carrier ([0156]) microparticles of uniform size distribution, wherein the at least one therapeutic agent is dispersed throughout each microparticle ([0157], claim 1). The microparticulate formulation comprises a powder suspension of microparticles which further comprise a slow-release compound, wherein the slow-release compound is a biodegradable polymer, wherein the biodegradable polymer is selected from the group consisting of polylactide-polyglycolide, poly(orthoester), and poly(anhydride) ([0332], claims 8-11).
MacDonald teaches the method wherein administering occurs via a surgical injection apparatus which is a needle (claims 12-13). MacDonald teaches a parenterally administered composition is delivered using a needle, e.g., a surgical needle. The term "surgical needle" as used herein, refers to any needle adapted for delivery of fluid (i.e., capable of flow) compositions into a selected anatomical structure ([0233]). Injectable preparations, such as sterile injectable aqueous or oleaginous suspensions, may be formulated according to the known art using suitable dispersing or wetting agents and suspending agents ([0233]). The flowable sustained release microparticulate composition is formulated in an injectable depot form and such formulations can be formulated with ion exchange resins ([0332]). Here the teachings of MacDonald illustrate a passing of the liquid dispersion through a needle for an injectable formulation.
It would be prima facie obvious to a person of ordinary skill in the art ahead of the effective filing date of the claimed invention to apply the method of using a needle to deliver formulations such as those of Phares comprising treprostinil resin particles because Macdonald teaches ion exchange resins ([0332]). Macdonald discloses prostacyclin as a vasodilator and the treatment of systemic vasoconstriction such as pulmonary hypertension ([0145]). Macdonald provides a means of administration that allows for the administration of a therapeutic amount that is lower than that is necessary when administered systemically in a sustained release formulation and may further prevent adverse health events, e.g., delayed cerebral ischemia (DCI) ([0351]).
Regarding claim 14, Phares does not mention delivering the composition more than once per day and therefore meets the limitation.
Regarding claim 17, Phares teaches treprostinil (abstract).
Regarding claim 18, Phares teaches that the amount of treprostinil that may be loaded onto an ion-exchange resin may range from 1% to 75% ([0032]) to read on the claimed 1-80% range.
Regarding claims 20 and 21, Phares teaches water insoluble coatings and does not teach resorbable. Macdonald teaches that according to some embodiments, delivery of the at least one therapeutic agent using microparticle technology involves bioresorbable, polymeric particles that encapsulate the at least one therapeutic agent and at least one additional therapeutic agent ([0308], [0380], [0452], [0517]). Macdonald teaches the Poly(lactide-co-glycolide) (PLGA) biodegradable polymer to read on the copolymer species of instant claim 21 and thereby read on instant claim 20. Additionally in paragraph [0312] of Macdonald, according to some embodiments, the at least one therapeutic agent is impregnated in or on a polyglycolide (PGA) matrix. Macdonald teaches that PGA is a linear aliphatic polyester developed for use in sutures and that studies have reported PGA copolymers formed with trimethylene carbonate, polylactic acid (PLA), and polycaprolactone; some of these copolymers may be formulated as microparticles for sustained drug release ([0312]). It would be obvious to incorporate the polymers of Macdonald in the treprostinil compositions and formulations of Phares because Macdonald teaches the bioresorbable biodegradable aspect that contributes to improved controlled-release/sustained-release of treprostinil.
Regarding claim 23, MacDonald teaches molecular weights from polymer enhances aqueous solubility of the microparticulate formulation ([0520]). MacDonald gives the examples of suitable polymers to include but are not limited to poly-(d-glutamic acid), and copolymers thereof; wherein polyglutamic acids having molecular weights between about 5,000 to about 100,000 ([0520]). Here the prior art reads on the claimed ratio and 10-200kDa.
Regarding claim 26, Phares teaches that the treprostinil-ion exchange resin composition thus prepared may be stored for future use or promptly formulated with conventional pharmaceutically acceptable carriers to prepare finished ingestible compositions for delivery orally, nasogastric tube, or via other means ([0047]). The compositions may, for example, take the form of liquid preparations such as suspensions, or solid preparations such as powders ([0047]).
Regarding claim 28, Phares teaches treating PAH ([0044]). MacDonald recognizes the treatment of PAH ([0145]).
Regarding claims 27 and 29 (0.65 mm, 0.85 mm), MacDonald teaches that according to some embodiments, the surgical injection apparatus is a needle; the surgical injection apparatus may have an 18 gauge ([0490]). As evidenced by Caltech, 18 G has an outer and inner diameter of 1.270 mm/0.838 mm and from the table shown larger gauges provide smaller diameters (page 1 of document). In light of these teachings one skilled in the art would optimize delivery and accordingly utilize the appropriate gauge needle depending on the particular site of entry of the subject. 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. MPEP2144.05(II)(A).
Regarding claims 31 and 32, Phares teaches that typically, the size of the ion-exchange resin particles is from about 5 microns to about 1000 microns ([0022]). Phares further teaches that in one embodiment the particles used in liquid dosage form can be within the range of about 40 microns to about 250 microns for liquid dosage forms to overlap with the claimed 20-150 microns ([0022]). Phares teaches pharmaceutical grade cholestyramine resin that is described as having a particle size in the range of 95% of less than 100 microns and 40% less than 50 microns ([0024]).
2. Claims 22 and 24 are rejected under 35 U.S.C. § 103 as being unpatentable over Phares et al. (US 2017/0095432 A1) in view of Macdonald et al. (US 20120245561 A1), and further in view of Shigeyuki et al. (US 6117455 A).
The teachings of Phares and MacDonald are discussed above.
Phares teaches that the organic matrix/release retardant and coatings may comprise water insoluble polymers. As mentioned above MacDonald teaches resorbable polymers. The references do not teach 90% resorbable within 6 months.
However, Shigeyuki discloses the use of a polymer that is slightly water-soluble or water-insoluble polymer having biocompatibility (column 7, line 57). Examples of the polymers include biodegradable polymers such as polylactic acid, polyglycolic acid, and polylactic acid caprolactone (column 7, line 58-61). Among these polymers, biodegradable polymers are particularly preferred for injections. In the case of lactic acid/glycolic acid copolymer (PLGA), for example, the biodegradability (i.e., degradability in living bodies) is defined as the percentage (w/w) of water-soluble low-molecular weight fragments degraded from PLGA based on PLGA and it should be more than 10% in one year after subcutaneous or intramuscular administration, preferably more than 80% in three months after subcutaneous or intramuscular administration. The biodegradable polymer is preferably a polyester. (See column 8, lines 12-21).
The teachings of Shigeyuki reads on the species of claim 21, and as such, a skilled artisan would reasonably expect the properties thereof would exhibit the same characteristics and functionalities wherein at least 90% would be resorbable within 6 months of administration. One would be motivated to apply the teachings of Shigeyuki to those of Phares and MacDonald because Shigeyuki teaches that the biodegradability of polyester polymers may reduce bleeding side effects and the microcapsule taught can be safely used to treat diseases in the circulatory system (e.g., thrombosis, transient cerebral ischemic attack, cerebral thrombosis (acute phase) (column 14, line 13). This complements Phares’ focus on improving controlled release of the drug and MacDonald’s concerns about cerebral ischemia ([0351]).
Response to Arguments
Applicants' arguments with respect to claims 14, 15, 17, 18, 20-24 and 26-32 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
Claims 14-15, 17-18, 20-24 and 26-32 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Karen A. Ketcham whose telephone number is (571)270-5896. The examiner can normally be reached M-F, 9-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ali Soroush can be reached at 571-272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Karen A Ketcham/Examiner, Art Unit 1614
/ALI SOROUSH/Supervisory Patent Examiner, Art Unit 1614
