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 .
Claim Status
Claims 14-15 and 17-32 are pending.
Claim 14 is currently amended.
Claims 1-13 and 16 are canceled.
Claims 19 and 25 are withdrawn.
Claims 14-15, 17-18, 20-24 and 26-32 have been examined.
Claims 14-15, 17-18, 20-24 and 26-32 are rejected.
Acknowledgement of Receipt
This Office Action is in response to the Applicant’s amendment and remarks filed 11/11/2024.
Information Disclosure Statement
The Information Disclosure Statement (IDS) submitted on 11/11/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, this IDS has been considered by the Examiner.
Withdrawn Rejections
In light of Applicant removing “only” in line 13 of claim 14, rejection of claim 14 under 35 U.S.C. § 112(a) as failing to comply with the written description requirement is withdrawn.
:
Maintained Claim Rejections - Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 14-15, 17-18, 20-24 and 26-32 rejected under 35 U.S.C. 112, first paragraph or 35 U.S.C. 112(a), as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventors, at the time the application was filed, had possession of the claimed invention.
Claim 14 recites “released directly to the site of injection.” Insufficient support is found in the instant application for releasing (treprostinil compound) “directly to the site of injection” as argued by applicants. The word “directly” is used three times in the instant specification in the context of carrier material changing performance characteristics (see Applicants’ Spec., [0093]), particle size dimension (see Applicants’ Spec., [0170]), and microparticle compositions (MPC) (see Applicants’ Spec., [0207]). Written description in this context is lacking support for the amended claim limitation since “directly” is not describing the release of drug compound relative to the injection site. Applicants argue that this limitation excludes the shell enclosing the particles of Canham. However, there is no support in the instant application for such an interpretation, and applicants have no support to exclude this feature of Canham. To the extent that this new limitation might be construed to exclude a shell, or other features, such as those of Canham, the above recitation of “released directly to the site of injection” in the claim 14 and dependent claims thereof is new matter and must be removed from the claims. For the purposes of this Office Action, this limitation will be considered to be met by local delivery of treprostinil at the site of injection.
Maintained 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.
Claims 14, 17-18, 20, 28, and 30-32 are rejected under 35 U.S.C. 103 as being unpatentable over Canham (WO 2014/165097, pub. Oct. 9, 2014).
Canham discloses a device in which a shell encloses a plurality of carrier particles that are porous and the active (e.g., drug) is disposed in said pores to be diffused out and delivered to a subject in need of the active (abstract; pg. 2, line 32; claim 1). Canham teaches that an excipient may be disposed outside the particles and inside the device’s shell such that the particles are suspended in solution and/or form a slurry (i.e., liquid dispersion) (pg. 21, lines 31-34; p. 34, lines 4-7). Canham teaches that carrier particles loaded with a liquid drug advantageously contribute to improved handling and cost savings for manufacturing (pg. 23, lines 21-24). In some embodiments, the liquid drug is treprostinil (pg. 23, lines 27-29). Canham teaches controlled and sustained release of agents (drugs) from the particles that treat pulmonary arterial hypertension (PAH) and ameliorate symptoms thereof (e.g., inflammation and rheumatic conditions) (pg. 23, lines 21-24; pg. 37, lines 10-18). The release rate of the drug is determined by the release of the drug from the pores of the carrier material (pg. 4, lines 10-11; claim 23). The devices advantageously localize administration to a desired area of the body (pg. 2, lines 16-18; pg. 36, lines 4-12).
Canham teaches that the device releases the beneficial substance for between about one month and one year when immersed in simulated body fluid, and wherein administering the device comprises injecting the device into the patient (i.e., administering by injection; sustained release) (pg. 38, lines 7-12; claims 35-37).
Regarding the biocompatible sustained-release limitation Canham teaches that the ) particles comprise a porous carrier material, a beneficial substance is disposed within pores of the carrier (pg. 2, lines 32-33), and that in some embodiments, the carrier material is resorbable or bio-erodible (pg. 4, lines 5-6). Amended claim 14 recites:
at least about 90% of the particles having a maximum diameter of between about 10 µm and about 200 µm; less than about 10% of particles of the composition having a maximum diameter that is more than about 50% greater than the average diameter of particles in the composition and less than about 10% of particles of the composition having a maximum diameter that is more than about 50% less than the average diameter of particles in the composition;.
Canham teaches that in certain embodiments, the particles of the device, measured at the largest diameter, have an average size of about 1 to about 500 microns, about 5 to about 100 microns, or about 5 to about 20 microns (pg. 12, lines 28-31; pg. 20, lines 13-14). Canham teaches that greater than 90% of the particles may have a particle size of from 1- 20 microns, (pg. 12, lines 31-33; pg. 20, lines 27-29).
Canham teaches that at least 80%, 90%, 99%, or even 100% of the particles in the device, measured at the largest diameter, are about 1 to about 500 microns, such as about 5 to about 500 microns, or about 2 to about 100 microns (pg. 20, lines 13-17). These teachings encompass or significantly overlap with the instantly claimed particle size range. Further, Canham teaches an average particle size of about 5 to about 100 µm, such as about 5-20 µm, and that greater than 90% of the particles may have a particle size from 1-20 (pg. 12, line 30 to pg. 13, line 2). Note that 50% greater than 10 µm is 15 µm, and 50% less than 10 microns is 5 µm. Further, Canham teaches a d10 in the range of 1-5 (meaning 10% of the particles have a diameter below 1-5 µm) and a d90 in the range of 10-20 µm (meaning 90% of the particles have a diameter below 10-20 µm). As such, Canham teaches embodiments that meet all the limitations of the instantly claimed particle sizes.
Regarding the “less than about 10% of particles of the composition having a maximum diameter that is more than about 50% less than the average diameter,” limitation, Canham’s teaching of d10 at 1-5 microns falls within the 50% less than about (5 µm) range. Furthermore, since Canham teaches that even 100% of the particles in the device can be about 2 to 100 microns (pg. 20, lines 15-17), that meets the “less than 10% of particles” limitation of claim 14. This teaching of Canham comports with the uniform distributions disclosed in the instant specification (see Applicants’ Spec., [0019], [0174]).
Canham teaches a treatment period of at least one day limitation by disclosing that effective amounts are released between 1 week to 1 year to read on the “sustained-release treatment period of at least one day” limitation (pg. 38, lines 7-9).
Lastly from amended claim 14, regarding the treprostinil compound being released directly to the site of injection, Canham teaches that the treprostinil is released directly to the target site for example into tumors (see top of pg. 36).
Regarding claims 17 and 30, Canham teaches prodrugs and treprostinil (pg. 22, lines 5-7; pg. 23, lines 28-29). Canham teaches that the device contains drug(s) to treat pulmonary arterial hypertension (pg. 37, line 10).
Regarding claim 18, Canham teaches that the load level of the carrier material is up to 70%, such as up to 40% by weight based on the combined weight of the carrier material and the beneficial substance (pg. 19, lines 25-26).
Regarding claim 20, Canham teaches that the carrier material is resorbable or bio-erodible (pg. 4, lines 5-6; claim 21).
Regarding claim 28, Canham teaches that one or more drugs may be used to treat pulmonary arterial hypertension (pg. 37, lines 10-11).
Regarding claim 31, Canham teaches that the particles, measured at the largest diameter, have an average size of about 5 to about 100 microns (pg. 12, line 30).
Regarding claim 32, Canham teaches that 100% of the particles may be about 1 to about 500 microns (pg. 20, lines 15-17).
In light of these teachings, it would have been prima facie obvious to a person of ordinary skill in the art, ahead of the effective filing date of the claimed invention, to use the particle size distribution, and treatment method(s) of Canham with treprostinil with expected results. Canham teaches that particles loaded with a liquid drug can be easier to handle than the liquid drug itself, further implying the cost saving benefits to the manufacture of controlled release devices that deliver liquid drugs (pg. 23, lines 21-24).
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Canham (WO 2014/165097, pub. Oct. 9, 2014) as applied to claims 14, 17-18, 20, 28, and 30-32 above, further in view of Leifer (WO 2014/085813, pub. Jun. 5, 2014).
The teachings of Canham are set forth above and are incorporated herein.
While Canham teaches long-term sustained release (e.g., for delivery on the order of years) and thus strongly suggests administration less than once a day, Canham does not expressly teach a delivery that is not more than once per day.
Leifer discloses particulate compositions including treprostinil formulations and methods for treating pulmonary hypertension (abstract, [0008]). Leifer teaches that the effectiveness of drugs for PAH is limited and compliance is a major issue for treprostinil patients ([0005-0008]). Leifer teaches injecting an effective amount of prostacyclin and a once-a-day dosing ([0018], [0023], [00116-00119], claims 96, 101, 108, 115, 117). The compositions reduce dose frequency from 4-times a day for currently approved prostacyclin (e.g., treprostinil) therapies to “1X daily” ([0027]).
It would have been prima facie obvious to a person of ordinary skill in the art, ahead of the effective filing date of the claimed invention, to administer the sustained delivery compositions of Canham once-a-day or less. One would be motivated to do so because Leifer provides a means to reduce patient burden and discomfort ([0027]) while improving patient compliance for more predictable outcomes ([00113-00115]). Further, one would not expect to administer Canham’s long-term sustained release compositions more than once a day.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Canham (WO 2014/165097, pub. Oct. 9, 2014) as applied to claims 14-15, 17-18, 20, 28, and 30-32 above, further in view of Leifer (WO 2014/085813, pub. Jun. 5, 2014), further in view of Zhang (US 2019/0010112, pub. Jan. 10, 2019).
The teachings of Canham and Leifer are set forth above and are incorporated herein.
Canham and Leifer do not teach particles themselves being comprised of a resorbable polyester polymer material carrier.
Zhang teaches treprostinil derivatives that are used to treat conditions responsive to treatment with treprostinil ([0117]). Zhang provides a composition that can be formulated as a depot that can be injected and can be designed to deliver the treprostinil derivative over at least about 1 week to 2 months or longer ([0111]). For example, a treprostinil derivative can be formulated with a polymeric material (e.g., polyglycolic acid [PGA], polylactic acid [PLA] or a copolymer thereof [e.g., PLGA]) ([0111]).
It would have been prima facie obvious to a person of ordinary skill in the art, ahead of the effective filing date of the claimed invention, to combine treprostinil with polyester polymeric material taught by Zhang in the carrier material of Canham in view of Leifer with predictable results. One would be motivated to do so because Zhang underscores that the material contributes to delayed or sustained release of the therapeutic agent ([0111]).
Claims 22-24, 26-27, and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Canham (WO 2014/165097, pub. Oct. 9, 2014) in view of Leifer (WO 2014/085813, pub. Jun. 5, 2014) and Zhang (US 2019/0010112, pub. Jan. 10, 2019) as applied to claims 14-15, 17-18, 20-21, 28, and 30-32 above, further in view of Shigeyuki (JP3790567, Jun. 28, 2006) with evidence from Wikidoc Needle Gauge Comparison chart pdf (2012).
The teachings of Canham, Leifer, and Zhang are set forth above and are incorporated herein.
Regarding claim 22, Canham, Leifer, and Zhang do not teach the 90% of particles are resorbable within 6 months.
Shigeyuki discloses an amorphous water-soluble physiologically active substance-containing microcapsule and a method for producing the same (Abstract). Shigeyuki discloses a polymer used in the present invention is a polymer that is hardly soluble or insoluble in water and biocompatible. Examples thereof include biodegradable poly fatty acid esters (e.g., polylactic acid, polyglycolic acid ([0032]). Among these polymer polymers, biodegradable polymer polymers are particularly preferred when used as injections ([0033]). In the case of lactic acid/glycolic acid copolymer (PLGA), for example, in the case of lactic acid/glycolic acid copolymer (PLGA), the biodegradability of the biodegradable polymer is defined by the ratio (w/w%) of PLGA to water-soluble low molecular weight fragments ([0033]).
Generally, it is 10% or more in one year after subcutaneous or intramuscular administration, and preferably 80% or more in 3 months after subcutaneous or intramuscular administration ([0033]). Of these glycolic acid copolymers, those having a relatively rapid degradation in vivo and a release period of less than one month when used alone are preferred ([0034]). In particular, a lactic acid / glycolic acid copolymer or a hydroxybutyric acid / glycolic acid copolymer is preferable ([0034]). The biodegradable polymer is preferably a polyester ([0033]). Since the particles in the prior art are made of the material claimed by instant claim 21, a person of ordinary skill would reasonably expect the use of said particles made from the same materials (i.e., those from instant claim 21) to have the same properties and/or exhibit the same characteristics and functionalities, i.e., wherein, on average, at least 90% are resorbable within 6 months of administration.
Regarding claim 23, Canham, Leifer, Zhang do not teach the polyester polymer is between 50 and 100 and the molecular weight of the polyester polymer is between 10 - 200kDa.
Shigeyuki discloses that the average molecular weight of the polymers are preferably 2,000 to about 800,000 (i.e., 2 – 800 kDa) and the ratio for lactic acid/glycolic acid is preferably 100/0 to 25/75 ([0035]). The ranges of the instant claim overlap or lie within those of Shigeyuki. In the case where the claimed ranges overlap or lie inside ranges disclosed by the prior art, a prima facie case of obviousness exists.
Regarding claim 24, Canham, Leifer, and Zhang do not teach the detectible amount of particles remaining in a patient 3 months or more.
Shigeyuki demonstrates that the sustained release-preparation of present invention can be administered to a blood mammal (i.e., patient) and exemplify embodiments with subcutaneous administration to rats and meet the requirements of the instant claim. Plasma concentrations are a well-known measured biomarker to detect amounts of particles (i.e., drug) in patients.
See Figure 1 which shows the plasma concentration (vertical axis) of compound A-containing microcapsules (i.e., particles) approaches zero over time (day) after administration [0070]. See Fig. 1 below.
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It would have been 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 exemplified embodiment of Shigeyuki to the embodiments of Canham, Leifer, and Zhang with predictable results. One would be motivated to do so because although Canham emphasize the need for customizable delivery of therapeutics is a need in drug delivery systems (pg. 1, line 33), Shigeyuki emphasizes how the biodegradability of polyester polymers (i.e., microcapsule) have a positive effect on patient safety (i.e., reduction in prolonged bleeding) ([0070]). And combination of the known method of formulating the polymers of Shigeyuki with polyesters such as PEG into the known particle of Canham which is ready for improvement of customized biodegradable and safe delivery would yield predictable results.
Regarding claim 26, Canham, Leifer, and Zhang do not teach the dry powder form adapted to form a suspension with a reconstitution diluent limitation.
Shigeyuki discloses examples of the preparation of present invention to include microcapsules used as a dispersant in aqueous suspension to form a sustained-release injection ([0050]). In the example an excipient is added and re-dispersed, and then frozen. When solidified by drying or spray drying and adding distilled water (i.e., diluent) for injection, a more stable sustained-release injection can be obtained ([0052]). See Example 1 in which microcapsules were obtained as a powder (i.e., dry powder form) ([0059]).
It would have been prima facie obvious to a person of ordinary skill in the art, ahead of the effective filing date of the claimed invention, to utilize the aqueous suspension aspect taught by Shigeyuki in the diluent of Canham in view of Leifer, and Zhang with a reasonable degree of predictable results. One would be motivated to do so since Shigeyuki provides an extended shelf-life and improved handleability ([0052]). Combining the known method of drying and reconstituting of Shigeyuki with water into the known modifiable carrier particles of Canham would yield predictable results.
Regarding claims 27 and 29, Canham teaches and suggests the inner or outer diameter (0.65 mm, 0.85 mm) limitation of claim 27 by disclosing disclose device of present invention may be shaped and sized for injection (e.g., less than about 0.5 mm in diameter, e.g., to fit through at least one of a needle having a size from about 30 gauge to about 15 gauge) (pg. 7, lines 24-27).
Canham doesn’t explicitly identify the diameter of 0.5 mm as being inner or outer. Evidence from the Wikidoc Needle Gauge Comparison chart shows that the needle of Canham would have an inner diameter of 0.159 mm (< 0.65) and an outer diameter of 0.3112 mm (< 0.85 mm) (see pdf, pgs. 1-2).
Canham, Leifer, and Zhang do not teach the method which comprises injecting the composition into the patients with a needle, the needle having an inner diameter of less than 0.65 mm, an outer diameter of no greater than 0.85 mm limitation of claim 29.
Shigeyuki discloses that the particle size of the microcapsules may be in a range satisfying the dispersibility and needle penetration when used as a suspension depending on the degree of sustained release, for example, an average diameter of about 0.5 to 400 μm (i.e., about 0.005 to 0.4 mm). More preferably, is the range of about 2 to 200 μm (i.e., about 0.002 to 0.2 mm) ([0049]). The prior art average diameters (i.e., 0.4 mm and 0.2 mm) meet the limitations of the instant claim.
It would have been prima facie obvious to a person of ordinary skill in the art, ahead of the effective filing date of the claimed invention, to utilize the diameter of the microcapsules (i.e., composition) taught by Shigeyuki in the device of Canham in view of Leifer, and Zhang. One would be motivated to do so since the diameters of Shigeyuki improve the ease of administration as injections ([0050]). Example 2 (i.e., lactic acid/glycolic acid copolymer) is administered subcutaneously at 20 mg/kg to SD rats (i.e., patient) ([0069]). The diameter of the needle used on the rats (i.e., patient) is not given. The diameters for the microcapsules and preparations are provided ([0049]). One of ordinary skill in the art would have expected predictable results by applying the dimensions of the microcapsules taught by Shigeyuki to the device of Canham in view of Leifer, and Zhang. Combining known microcapsules of known diameters of Shigeyuki with the known carrier particles of Canham which are ready for improvement of easy administration for injections, would yield predictable results.
Response to Arguments
Applicants’ arguments filed 11/11/2024 have been considered but are not persuasive.
35 USC 112
Applicants argue that Figure 3 demonstrates particles of the invention as they exit a 27G needle citing paragraphs [0025] and [0225] as support for “treprostinil compound is released directly to the site of injection from the biocompatible sustained-release treprostinil compound particles” (see Remarks, pg. 6, last sentence). Applicants argue the particles are biocompatible with the living tissue with which the particles come in contact as they are administered (see Remarks, pg. 7, para. 1).
The Examiner respectfully argues that Applicants providing the figure with a caption that reads, “Treprostinil particles shown in contact with the needle tip,” does not support the recitation of “the treprostinil compound is released directly to the site of injection” in line 12 of claim 14. Generally releasing a compound directly to the intended area (the injection site) implies administration without delay by an intermediate step or anything that would impede or interrupt absorption. The instant specification does not appear to mention a “site of injection” or describe a level of treprostinil compound absorbed with respect to delivery performance. Releasing particles that incorporate Treprostinil is not the same as releasing the compound of Treprostinil. It is well known in the art that particles comprising active compounds can be coated to have delayed release.
Applicant’s description of particles that are injectable “to mean that the particles can be formulated in a dispersion by contact with one or more suitable diluents/solvents and the dispersion formulation delivered through an injection system, such as a needle delivery system, to the tissues of a mammalian subject” (see Spec., [0082]). As described, an administration by injectable delivery requires particles coming in contact with other elements that play a role in facilitating the administration of the compound, indicating an intermediate step and thus, contrary to the release of the treprostinil compound directly to the site.
35 USC 103
Applicant argues that Canham’s shell and carrier particles are porous with drug diffusing out of the particles into a space within the shell, contrasts with “treprostinil compound is released directly to the site of injection” in claim 14 (see Remarks, pg. 9, para. 4).
The claims as presented do not exclude the shell of Canham, and are considered to “directly” release drug to the site of injection, as they are suitable for local delivery (i.e., directly to the area where the particles are injected). Further, as discussed above, applicants are not supported for the amendment. Moreover, Applicants describe treprostinil being “released from microparticles and/or nanoparticles upon administration to the patient, that is upon exposure to the physiological environment of the patient’s body” (see Applicants’ Spec., [0191]). Canham teaches that the active diffuses from the particle to a local site of injection to include “directly into tumors” found on line 1 of page 36 (pg. 2, lines 16-17; pg. 6, lines 11-14).
Applicant argues that the beneficial substance of Canham is released from the device into the patient after administration and teaches away from administration other than by the use of the shell device (see Remarks, pg. 10, para. 3). Applicant argues Canham requires a shell device to control the release of API (pg. 16, para. 1).
Applicants describe various carriers as “carrier means” e.g., “means for facilitating long acting release” (see Spec., [0273]). Canham teaches a device comprising a shell (e.g., tube) enclosing a plurality of particles which would be immediately recognized as a carrier system and/or a configuration of particles to one of ordinary skill in the art (see Canham, abstract). Canham teaches a shell that advantageously protects the carrier and beneficial substance against degradation in the patient’s body, during the manufacturing process, during storage, and helps stabilize the beneficial substance over the course of treatment (see Canham, pg. 2, lines 19-29). Not only is Canham’s teaching of carrier material (i.e., a plurality of particles) compatible with Applicants’ disclosure of carriers, but also demonstrates how the material advantageously holds and gradually releases a beneficial substance (See Canham, pg. 12, lines 14-16). The shell of Canham is considered to read on a carrier system within the meaning of the instant claims.
Applicants argue that the office action effectively “cherry picked” treprostinil from Canham’s disclosure of “beneficial substances” (see Remarks, pg. 11, no. 2) and that impermissible hindsight was applied (see Remarks, pg. 11 – pg. 12 para. 1). Applicants argue Canham describes the use of relatively larger pore size compositions for high molecular weight molecules and smaller pore size compositions for molecules of lower molecular weight while the molecular weight of treprostinil is only 390 Daltons (see Remarks, pg. 15, para. 2).
The Examiner asserts that to analyze the patentability of a claimed invention under Section 103, as Applicants have pointed out, obviousness inquiries are performed somewhat in “hindsight” and involves regarding the art as a whole (see Remarks, pg. 12, para. 1). Further, MPEP 2145(X.)(A.) states that as long as knowledge which was within the level of ordinary skill at the time the claimed invention was made is taken in account, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. Canham teaches the use of drugs i.e., treprostinil, to treat pulmonary arterial hypertension (pg. 23, line 29), combined with the teaching that particles loaded with a liquid drug can be easier to handle than the drug itself (pg. 23, lines 21-24) would be immediately recognized as contribution to the art to one of ordinary skill in the art. Looking to lines 28-29 on page 23, Canham teaches the liquid drug is prostacyclin or a prostacyclin analog such as treprostinil, iloprost, or beraprost. As evidenced by Skoro-Sajer (Optimal use of treprostinil in pulmonary arterial hypertension: a guide to the correct use of different formulations. Drugs. 2012 Dec 24;72(18):2351-63), intravenous prostacyclin has developed due to its favorable properties, including longer half-life, chemical stability, the possibility of intravenous infusion without the need for ice packs, and easy drug preparation (abstract). As further evidenced by Skoro-Sajer, treprostinil is the only prostacyclin with different options of delivery, and intravenous treprostinil improves exercise capacity, functional class and hemodynamics in patients with PAH (abstract). It is the combination teachings in the prior that show the obviousness of treprostinil.
Applicants’ pore size argument is not effective to rebut a motivation to combine. he Examiner asserts that Canham’s discussion of preselecting pore size to control the release rate of the beneficial substance (pg. 16, lines 30-31) would be a well-known technique in the art. Canham goes on to describe other parameters e.g., molecular radius of the beneficial substance, to control the release rate in a biological system (pg. 17, lines 10-11). Canham further discusses the need to prevent aggregation as it will impede the controlled release (pg. 17, lines 22-33). These teachings apply to the objective and discretion of the skilled artisan. MPEP 2144.05(II.)(A.) states that "[W]here 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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).Applicant argues that the teachings of Leifer in view of Zhang and Shigeyuki with evidence from Wikidoc does not make up for the failure of Canham to teach, suggest, or render the claimed invention obvious.
There are many reasons to combine the teachings of the prior art. Zhang provides an improvement to extended/sustained release of the therapeutic agent ([0111]). Shigeyuki emphasizes how the biodegradability of polyester polymers (i.e., microcapsule) have a positive effect on patient safety (i.e., reduction in prolonged bleeding) ([0070]), while improving upon the ease of administration as injections ([0050]) and handleability ([0052]). Wikidoc provides evidence of the parameters of the needle of Canham (see pdf, pgs. 1-2). Leifer provides a means to reduce patient burden and discomfort ([0027]) while improving patient compliance for more predictable outcomes ([00113-00115]).
For these reasons, Applicants’ arguments are found unpersuasive. The rejections are therefore maintained.
Conclusion
All claims under consideration remain rejected; 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 mailing date of this final action.
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/Karen A. Ketcham/Examiner, Art Unit 1614
/ALI SOROUSH/Supervisory Patent Examiner, Art Unit 1614
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