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 .
Receipt is acknowledged of Amendments and Remarks filed on 05/11/26. Claims 1, 18-19 and 32 have been amended, no claims have been cancelled and new claim 34 has been added. Accordingly, claims 1, 6-8, 18-19 and 32-34 are under examination on the merits. Claims 11-17 remain withdrawn.
Rejections and/or objections not reiterated from the previous Office Action are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
Priority
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AlA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No.15/418,388 or its provisional Application No. 62/289,095, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
This Application is a CIP of 15/418,388 filed on 01/27/2017 claiming benefit of 62/289,095 filed on 01/29/2016. However, the ‘388 Application fails to provide support for claims, because there is no support for at least the “amount of up to 200 ug” or “from about 1 µg to about 180 µg”. Thus, the priority awarded to the claims is 06/07/2018.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 34 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 34 recites a limitation related to the effect of the dry powder in a subject after administration, but fails to further limit the scope of its parent claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. 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.
Applicant’s claims:
A drug delivery system comprising a dry powder inhaler and an inhalable pharmaceutical dry powder composition for breath-powered pulmonary delivery comprising spray-dried, hollow, porous microcrystalline particles that do not self-assemble, said microcrystalline particles comprising fumaryl diketopiperazine or a salt thereof, and from about 1% to about 5% (w/w) treprostinil or a pharmaceutically acceptable salt thereof, wherein the porous microcrystalline particles have a residual water content of 0.4%, a specific surface area ranging from about 59 m2/g to about 63 m2/g, and wherein the porous microcrystalline particles have a pore size ranging from about 23 nm to about 30 nm, the porous microcrystalline particles have an average pore volume of about 0.43 cm3/g, and up to about 92% of the microcrystalline particles have a volumetric median geometric diameter of less than or equal to 5.8 um and further wherein the inhalable pharmaceutical dry powder composition is provided in a reconfigurable disposable cartridge or capsule for a single inhalation comprising about 1 µg to about 200 µg treprostinil or a pharmaceutically acceptable salt thereof, wherein said cartridge or capsule comprises a lid and a cap which are movable relative to one another in a transitional motion.
Claim interpretation:
Claims 1 and 19, include the recitation of a disposable cartridge or capsule. The Specification does not appear to explicitly support “a disposable cartridge or capsule”. However, as it is typically known that capsules and cartridges in an inhaler are unit doses and are by definition disposable, the said limitation is not given a new matter rejection. Similarly, it is interpreted that the prior art disclosing a unit dose, cartridge or capsule containing a powder formulation for inhalation, meets the limitation of disposable.
Claims 1, 6-8, 18-19 and 32-34 are rejected under 35 U.S.C. 103 as being unpatentable over Wilson et al (WO 2014144895) in view of Tarara et al (US 20100272823), Baker et al (WO 2009152160) and Smutney et al (WO 2009152477), Leonard et al (20040092470) and as evidenced by Olschewski et al (US 20080200449).
Wilson et al teach DKP microcrystals made by an improved method where they do not irreversibly self-assemble into microparticles. The microcrystals can be dispersed by atomization and re-formed by spray drying into particles having spherical shell morphology. Active agents and excipients can be incorporated into the particles by spray drying a solution containing the components to be incorporated into microcrystalline diketopiperazine particles. In particular, the microcrystalline particle compositions are suitable for pulmonary drug delivery of one or more peptides, proteins, nucleic acids and/or small organic molecules (see Abstract).
Disclosed are powders comprising a plurality of substantially uniform, microcrystalline particles, wherein the particles have a substantially hollow spherical structure and comprise a shell which can be porous, and comprises crystallites of a diketopiperazine that do not self-assemble (see [0007]-[0008]).
In a particular embodiment, up to about 92% of the microcrystalline particles have a volumetric median geometric diameter of < 5.8 μm. The said particle's shell is constructed from interlocking diketopiperazine crystals having one or more drugs adsorbed on their surfaces. In some embodiments, the particles can entrap the drug in their interior void volume and/or combinations of the drug adsorbed to the crystallites' surface and drug entrapped in the interior void volume of the spheres (See [0009]).
Wilson et al disclose that the said dry powder inhaler system comprises a predetermined mass flow balance within the inhaler, wherein the inhaler conduits are designed to have varied flow distribution during an inhalation. For example, a flow balance of approximately 10% to 70% of the total flow exiting the inhaler and into the patient is delivered by one or more dispensing ports, which airflow passes through an air conduit designed with an area for containing a powder formulation, and wherein approximately 30% to 90% air flow is generated from other conduits of the inhaler during an inhalation maneuver. Flow rates ranging from about 7 to 70 liters per minute result in greater than 75% of the container or the cartridge contents dispensed in fill masses between 1 and 50 mg. Disclosed is an inhalation system which can emit a respirable fraction/fill of a powder dose at percentages greater than 40% in a single inhalation, greater than 50%, greater than 60%, or greater than 70% (See [0039]).
Regarding the rf/fill value, Wilson et al disclose that the respirable fraction on fill (rf/fill) can be greater than 50%. In an exemplary embodiment, a respirable fraction on fill can be up to about 80%, wherein about 80% of the fill is emitted with particle sizes < 5.8 μm as measured using standard techniques (See [0062]).
Formulations of FDKP particles having a defined specific surface area less than 67 m2/g also provide dry powders for inhalation with acceptable aerodynamic properties (see [0078]). In Table 5 the specific surface area of one of the powders is 58.66 m2/g.
Wilson et al disclose that the said microcrystalline particles can comprise one or more active agents/drugs. The active agents can fall under a variety of biological activity and classes, such as vasoactive agents, hormones, prostaglandins including PG-12, proteins, etc, (See [0083]).
The drug content to be delivered on microcrystalline particles formed from FDKP can typically be greater than 0.01 % (w/w), e.g. from about 0.01 % (w/w) to about 75 % (w/w) (See [0084]).
The stability of the particle can be enhanced by small amounts of a surfactant, such as polysorbate-80, in the DKP solution from which the particles are precipitated (See [0071] and claim 15). The compositions may also comprise a carrier, including amino acids such as leucine, isoleucine, lactose, trehalose, and the like (See [0036]).
Wilson et al disclose drug delivery systems comprising an inhaler with or without a cartridge, wherein the cartridge is a unit dose dry powder medicament container comprising the particles disclosed herein and an active agent. The delivery system for use with the dry powders includes an inhalation system comprising a high resistance inhaler having air conduits which impart a high resistance to airflow through the conduits for deagglomerating and dispensing the powder.
Wilson et al disclose an inhalation system comprising a dry powder inhaler, a dry powder formulation comprising microcrystalline particles of fumaryl diketopiperazine having an FDKP trans isomer content between 45% and 65% and one or more than one active agents, the dry powder formulation being in a unit dose cartridge. Alternatively, the dry powder formulation can be preloaded in the inhaler (See [0039]-[0041]).
Wilson et al do not expressly disclose the pore size or pore volume of the said porous particles, the water content of the particles, the specific excipients of claim 7, the breath-powered delivery, the amount of dry powder in a single inhalation, treprostinil being the active agent/drug or its amounts and the cartridge or capsule containing a lid and cup. These are well known in the art as taught by Tarara et al, Baker et al, Smutney et al and Leonard et al and as evidenced by Olschewski et al.
Tarara et al teach a pulmonary delivery medicament comprising a plurality of particulates, the particulates comprising a structural matrix and a water insoluble and/or crystalline active agent. The said pulmonary delivery of bioactive agents is to selected physiological target sites using perforated microstructure powders (See abstract and [0014]).
Tarara et al disclose “By way of contrast, the present invention uses methods and compositions that yield powder formulations having extraordinarily low bulk density, thereby reducing the minimal filling weight that is commercially feasible for use in dry powder inhalation devices. That is, most unit dose containers designed for DPIs are filled using fixed volume or gravimetric techniques (See [0052]).
Tarare et also disclose that “DPIs generally rely entirely on the patient's inspiratory efforts to introduce a medicament in a dry powder form to the lungs” (See [0004]).
It is further disclosed that most devices are manually actuated, but some devices exist which are breath actuated. Breath actuated devices work by releasing aerosol when the device senses the patient inhaling through a circuit (See [0170]).
The said structural matrix defining the perforated microstructure may comprise cyclodextrins, polyacrylates, methylcellulose, polyanhydrides, etc, (See [0064]).
The said particulate formulations may comprise additives including carriers and surfactants such as lactose, sucrose, sodium chloride, sodium citrate, mannitol, polyoxyethylene (20) sorbitan monolaurate, etc, (See [0059]-[0066]).
Tarara et al teach that the said perforated microstructure defined by the structural matrix comprises a spray dried hollow porous microsphere incorporating at least one surfactant. It will further be appreciated that, by altering the matrix components, the density of the structural matrix may be adjusted. The said perforated microstructures preferably comprise at least one active or bioactive agent (See [0054]).
It is disclosed that the said active agent may be of antiallergics, bronchodilators, pulmonary lung surfactants, analgesics, antibiotics, antiinfectives, leukotriene inhibitors or antagonists, antihistamines, antiinflammatories, antineoplastics, anticholinergics, anesthetics, antituberculars, cardiovascular agents, enzymes, steroids, genetic material, viral vectors, antisense agents, proteins, peptides and combinations thereof (See [0034] and Claim 42).
Tarara et al disclose that the mean porosity (i.e. the percentage of the particle surface area that is open to the interior and/or a central void) of the perforated microstructures may range from about 0.5% to about 80%. As to the pores themselves, they typically range in size from about 5 nm to about 400 nm with mean pore sizes preferably in the range of from about 20 nm to about 200 nm. It is significantly advantageous that the pore size and porosity may be closely controlled by careful selection of the incorporated components and production parameters (See [0115]).
Baker et al teach phenylphosphonate prodrugs comprising one or more prostacyclins for the treatment of pulmonary arterial hypertension, and for delivery by aerosolization or dry powder (See abstract).
Disclosed is a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula I, or a pharmaceutically acceptable salt thereof, as a liquid or solid dosage form suitable for nebulization, pressurized metered dose inhalation or dry powder delivery (See Summary and claim 33).
An example of the compounds of formula I is treprostinil (See Page 65, Example 17).
A compound of Formula I or a pharmaceutically acceptable salt thereof, is delivered as a dry inhalable powder. The said compounds are administered endobronchially as a dry powder formulation to efficaciously deliver fine particles of compound into the endobronchial space using dry powder or metered dose inhalers. For delivery by DPI, the compound of Formula I is processed into particles with, predominantly, MMAD between about 1 μm and about 5 μm by milling spray (See page 36, 2nd para to Page 37, 2nd para).
Baker et al disclose a compound of Formula I, or a pharmaceutically acceptable salt thereof, is dosed in a therapeutically effective amount ranging from about 10 to about 5000 μg. The dose will be determined by the host treated and the severity of the disease as determined by those physicians skilled in the art. Preferably, the drug will be administered four, three, two, or most preferably once a day. In another aspect of the invention, a combination of an aerosol formulation of a compound of Formula I and a device significantly enhances the efficiency and speed of drug administration (See Page 37, last para and claims 35-36).
Disclosed is a compound of Formula I or a pharmaceutically acceptable salt thereof, delivered as a dry inhalable powder administered endobronchially as a dry powder formulation to efficaciously deliver fine particles of compound into the endobronchial space using dry powder or metered dose inhalers (See Page 36, lines 11-18).
Smutney et al teach a breath-powered, dry powder inhaler, a cartridge and a pulmonary-drug delivery system. are provided. The inhaler and/or cartridge can be provided with a drug delivery formulation comprising a diketopiperazine and an active ingredient. The device is easy to manufacture, provides a pre-metered single unit dose, it is relatively easy to use, and can be reusable or disposable (See abstract).
It is disclosed that the said cartridges can be structurally configured to contain a dose of, for example, from 0.1 mg to about 50 mg of a dry powder formulation, particularly about 20 mg of a powder composition (See [0168] and claim 44).
Smutney et al further teach that the said microparticles having a diameter of between about 0.5 and about 10 microns can reach the lungs, successfully passing most of the natural barriers. DKP microparticles with a specific surface area (SSA) of between about 35 and about 67 m2/g exhibit characteristics beneficial to delivery of drugs to the lungs such as improved aerodynamic performance and improved drug adsorption (See [000201] and [000216]).
Smutney et al also disclose a dry powder inhaler comprising a cartridge and wherein the cartridge comprises a container and a lid or cover, wherein the container can be movable relative to the lid or the lid can be movable on the container and can attain various configurations depending on its position, for example, a containment configuration, a dosing configuration or after use configuration. The container is cup-like (See [00019], [00021] and [00126]). It is further disclosed that “in this embodiment, container 151 or lid 156 can be movable, for example, by translational movement upon top 156, or top 156 can be movable relative to the container 151” (See [000158]).
Leonard et al teach a dry powder formulation consisting essentially of an oligo of particle size about 0.1µ to about 100 µ in diameter for treatment of numerous diseases and conditions by administration into the respiratory tract (See abstract, [0011] and claim 1). The said formulation is delivered via a suitable delivery device including dry powder inhalers (DPI) and metered dose inhaler (MDI) (See [0014]).
Leonard et al further teach that the term "dry" means that the formulation has a moisture content such that the particles are readily dispersible in a dry powder inhalation device to form an aerosol or spray. This moisture content is generally less than about 1% w/w, or less than about 0.5% w/w (See [0040]).
As evidenced by:
Olschewski et al teach treprostinil can be administered using a metered dose inhaler (See abstract).
It is disclosed that a metered dose inhaler in the present context means a device capable of delivering a metered or bolus dose of respiratory drug, such as treprostinil, to the lungs. One example of the inhalation device can be a pressurized metered dose inhaler. The inhalation device can be also a dry powder inhaler (See [0040]-[0041] and claims 3 and 21).
It would have been prima facie obvious to a person of ordinary skilled in the art at the time the invention was made to have combined the teachings of Baker et al, Tarara et al and Smutney et al with that of Wilson et al and as evidenced by Olschewski et al to arrive at the instant invention.
It would have been obvious to do so because Wilson et al teach dry powder formulations comprising crystalline microparticles of diketopiperazine (DKP), an active agent such as a prostaglandin and additives delivered via a dry powder inhaler. It is disclosed that the said crystalline microparticles preferably have a specific surface area of less than 67 m2/g, such as about 58.66 m2/g, which exhibit characteristics beneficial to delivery of drugs to the lungs such as improved aerodynamic performance. Wilson et al also disclose other characteristics of the said particles including rf/fill of greater than 50% and a volumetric median geometric diameter of < 5.8 µm.
Wilson et al’s disclosure is also to particles that do not self-assemble and are spray-dried hollow porous particles comprising an active agent such as a prostaglandin.
Tarara et al provide guidance on the pore size and pore volume of spray dried porous particles for inhalation by a breath actuated inhaler and suitable excipients including lactose and mannitol.
Baker et al teach dry powder formulations comprising a compound of formula I, i.e. prostacyclins, such as treprostinil, wherein the administered dose can be from 1 to 5000 µg.
Smutney et al also teach a breath-activated dry powder inhalation system comprising a cartridge, wherein the cartridge contains a container (cup) and a lid, and a formulation comprising DKP and an active agent and contain about 20 mg of the said dry powder.
Regarding the limitation of water content less than 0.4%, Leonard et al teach that a dry powder composition for inhalation generally has low moisture content preferably less than 0.5%.
As evidenced by Olschewski et al, Treprostinil can be effectively prepared in a dry powder dosage form and delivered to the lung via dry powder inhalation.
All references teach dry powder formulations comprising an active agent and suitable excipients/carriers. Porous microcrystalline DKP particles carrying an active agent are disclosed. Treprostinil is a known active agent suitable for treating disorders such as pulmonary hypertension and is known to be in its crystalline form. It is also known in the art to incorporate diketopiperazine for better absorption of an active agent. It is further known in the art that suitable pore size and pore volume of a perforated microstructure are effective in drug delivery to the pulmonary system. Other additives and particle characteristics such as surface area and geometric diameter are also well known in the art as shown. It would also be obvious to one of ordinary skill in the art to have looked in the art for guidance on particle and inhaler specifics such as cartridge content amount as taught by Smutney et al.
In other words, the claims would have been obvious because the technique for improving a particular formulation was part of the ordinary capabilities of a person of ordinary skill in the art, in view of the teaching of the technique for improvement in other situations. That is one of ordinary skill in the art is more than motivated to incorporate compounds and characteristics that are well known and disclosed for their advantages in the art to the compositions comprising treprostinil with a reasonable expectation of success.
As taught by the references and evidenced by at least Tarara et al, the DPI of Wilson et al is expected to be a breath-actuated (breath-powered) inhaler/device.
Claims 1, 6-8, 18-19 and 32-34 are rejected under 35 U.S.C. 103 as being unpatentable over Wilson et al (WO 2014144895) in view of Tarara et al (US 20100272823), Smutney et al (WO 2009152477), Leonard et al (US 20040092470), Olschewski et al (US 20080200449) and Roscigno et al (WO 2017192993).
Wilson et al, Tarar et al, Smutney et al and Leonard et al’s teachings are delineated above and incorporated herein.
The combined references lack a specific disclosure on the active agent being treprostinil or its dosage or the amount of powder in a single dose. These would have been an obvious modification in view of the teachings of Olschewski et al and Roscigno et al.
Olschewski et al teach treprostinil can be administered using a metered dose inhaler (See abstract).
It is disclosed that a metered dose inhaler in the present context means a device capable of delivering a metered or bolus dose of respiratory drug, such as treprostinil, to the lungs. One example of the inhalation device can be a pressurized metered dose inhaler. The inhalation device can be also a dry powder inhaler (See [0040]-[0041] and claims 3 and 21).
Roscigno et al teach a dry powder inhalation treatment for pulmonary arterial hypertension includes a dose of dry particles comprising greater than 25 micrograms of treprostinil enclosed in a capsule. The dry particles can include treprostinil, a wetting agent, a hydrophobicity modifying agent, a pH modifying agent and a buffer and a method of treating a patient via a dry powder inhaler (See Abstract, [0015], [00104] and claims 8-11).
It is disclosed that the said dose of dry particles comprises greater than or equal to 150 micrograms (µg) of treprostinil. The said dose of dry particles comprises greater than or equal to 5 mg, 10 mg or 15 mg of the dry particles (See [0015] and claims 1-6).
The said powder formulations may also comprise excipients including lactose, trehalose, polysorbate-80, L-leucine, sodium chloride, etc, (See [0061]-[0062]).
It would have been prima facie obvious to a person of ordinary skilled in the art at the time the invention was made to have combined the teachings of Olschewski et al, Roscigno et al, Smutney et al, Leonard et al and Tarara et al with that of Wilson et al et al to arrive at the instant invention.
It would have been obvious to do so because Wilson et al teach dry powder formulations comprising crystalline microparticles of diketopiperazine (DKP), an active agent such as a prostaglandin and additives delivered via a dry powder inhaler. It is disclosed that the said crystalline microparticles preferably have a specific surface area of less than 67 m2/g, such as about 58.66 m2/g, which exhibit characteristics beneficial to delivery of drugs to the lungs such as improved aerodynamic performance. Wilson et al also disclose other characteristics of the said particles including rf/fill of greater than 50% and a volumetric median geometric diameter of < 5.8 µm.
Wilson et al’s disclosure is also to particles that do not self-assemble and are spray-dried hollow porous particles comprising an active agent such as a prostaglandin.
Tarara et al provide guidance on the pore size and pore volume of spray dried porous particles for inhalation by a breath actuated inhaler and suitable excipients including lactose and mannitol.
Smutney et al also teach a breath-activated dry powder inhalation system comprising a cartridge, wherein the cartridge contains a container (cup) and a lid, and a formulation comprising DKP and an active agent and contain about 20 mg of the said dry powder.
Regarding the limitation of water content less than 0.4%, Leonard et al teach that a dry powder composition for inhalation generally has low moisture content preferably less than 0.5%.
Olschewski et al teach dry powder compositions comprising treprostinil delivered by a dry powder inhaler. Roscigno et al teach dry powder formulations comprising treprostinil, wherein the administered dose can be 150 µg or greater delivered to the lung via a dry powder inhaler, and wherein the unit dose may contain greater than 15 mg of the dry powder formulation.
All references teach dry powder formulations comprising an active agent and suitable excipients/carriers. Porous microcrystalline DKP particles carrying an active agent are disclosed. Treprostinil is a known active agent suitable for treating disorders such as pulmonary hypertension and is known to be in its crystalline form. It is also known in the art to incorporate diketopiperazine for better absorption of an active agent. It is further known in the art that suitable pore size and pore volume of a perforated microstructure are effective in drug delivery to the pulmonary system. Other additives and particle characteristics such as surface area and geometric diameter are also well known in the art as shown.
In other words, the claims would have been obvious because the technique for improving a particular formulation was part of the ordinary capabilities of a person of ordinary skill in the art, in view of the teaching of the technique for improvement in other situations. That is one of ordinary skill in the art is more than motivated to incorporate compounds and characteristics that are well known and disclosed for their advantages in the art to the compositions comprising treprostinil with a reasonable expectation of success.
As taught by the references and evidenced by at least Tarara et al, the DPI of Wilson et al is expected to be a breath-actuated (breath-powered) inhaler/device.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 6-8, 18-19 and 32-34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 3 and 5-10 of U.S. Patent No. 10,772,883 in view of Baker et al (WO 2009152160), Smutney et al (WO 2009152477), Tarara et al (US 20100272823) as evidenced by Leonard et al (US 20040092470). An obviousness-type double patenting rejection is appropriate because while the conflicting claims are not identical, the examined claims are not patentably distinct from the reference claims because the examined claims would have been obvious over the reference claims in view of Baker et al, Smutney et al and Tarara et al and as evidenced by Leonard et al.
The examined claim 1 is directed to a drug delivery system comprising a dry powder inhaler and an inhalable pharmaceutical dry powder composition for breath-powered pulmonary delivery comprising spray-dried, hollow, porous microcrystalline particles that do not self-assemble, said microcrystalline particles comprising fumaryl diketopiperazine or a salt thereof, and from about 1% to about 5% (w/w) treprostinil or a pharmaceutically acceptable salt thereof, wherein the porous microcrystalline particles have a specific surface area ranging from about 59 m2/g to about 63 m2/g, and wherein the porous microcrystalline particles have a pore size ranging from about 23 nm to about 30 nm, the porous microcrystalline particles have an average pore volume of about 0.43 cm3/g, and up to about 92% of the microcrystalline particles have a volumetric median geometric diameter of less than or equal to 5.8 um and further wherein the inhalable pharmaceutical dry powder composition is provided in a disposable cartridge or capsule for a single inhalation comprising from about 1 µg to 200 µg Treprostinil or a pharmaceutically acceptable salt thereof, wherein said cartridge comprises a lid and a cap which are movable relative to one another in a transitional motion.
Reference claims are directed to a dry powder pharmaceutical composition comprising inhalable 3,6-di(N-fumaryl-4-aminobutyl)-2,5-diketopiperazine microparticles; wherein each of the microparticles has a specific surface area of 35 m2/g to about 67 m2/g and comprises an active agent and the active agent is present at about 0.1 to about 20% by weight of the microparticles. The active agent may be a prostaglandin.
The differences are that the reference claims do not expressly disclose the active agent being treprostinil, the amount of it, microparticles comprising porous microcrystalline particles or the pore size or specific surface area or the specifics of the inhaler including the cartridge. However, the missing limitations are obvious to one of ordinary skill in the art as taught by Baker et al, Smutney et al and Tarara et al. Baker et al teach compositions comprising treprostinil and its single dose for inhalation and Tarara et al teach porous microcrystalline cellulose, a pore size of from about 20 nm to about 200 nm and a high porosity (i.e. pore volume) which are suggested for drug delivery to the pulmonary system. Smutney et al also teach a breath-activated dry powder inhalation system comprising a cartridge, wherein the cartridge contains a container (cup) and a lid, and a formulation comprising DKP and an active agent and contain about 20 mg of the said dry powder. As evidenced by Leonard et al, a dry powder formulation contains less than 0.5% water (moisture).
Accordingly, examined claims and reference claims in view of Baker et al, Smutney et al and Tarara et al and as evidenced by Leonard et al are so close that they are not patentably distinct.
Claims 1, 6-8, 18-19 and 32-34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-15 of U.S. Patent No. 9,393,372 in view of Baker et al (WO 2009152160), Smutney et al (WO 2009152477), Tarara et al (US 20100272823) and as evidenced by Leonard et al (US 20040092470). An obviousness-type double patenting rejection is appropriate because while the conflicting claims are not identical, the examined claims are not patentably distinct from the reference claims because the examined claims would have been obvious over the reference claims in view of Baker et al, Smutney et al and Tarara et al and as evidenced by Leonard et al.
The examined claim 1 is delineated above.
Reference claim 1 is drawn to an inhalation system comprising a dry powder inhaler comprising a mouthpiece and a container, wherein the container comprises a top and a bottom which are movable relative to one another, and wherein 20-70% of the total air flow through the inhaler enters and exits the container, a second flow path for 30-80% of the volume of air through the inhaler, wherein the inhalation system is configured to deliver the diketopiperazine to the pulmonary circulation of a subject, and said diketopiperazine is measured in a subject's plasma having an AUC greater than 2,300 ng*min/mL per mg of diketopiperazine content in the dry powder formulation.
The differences are that the reference claims do not expressly disclose the active agent being treprostinil, the amount of it, microparticles comprising porous microcrystalline particles or the pore size or specific surface area or the specifics of the inhaler including the cartridge. However, the missing limitations are obvious to one of ordinary skill in the art as taught by Baker et al, Smutney et al and Tarara et al. Baker et al teach compositions comprising treprostinil and its single dose for inhalation and Tarara et al teach porous microcrystalline cellulose, a pore size of from about 20 nm to about 200 nm and a high porosity (i.e. pore volume) which are suggested for drug delivery to the pulmonary system. Smutney et al also teach a breath-activated dry powder inhalation system comprising a cartridge, wherein the cartridge contains a container (cup) and a lid, and a formulation comprising DKP and an active agent and contain about 20 mg of the said dry powder. As evidenced by Leonard et al, a dry powder formulation contains less than 0.5% water (moisture).
Accordingly, examined claims and reference claims in view of Baker et al, Smutney et al and Tarara et al and as evidenced by Leonard et al are so close that they are not patentably distinct.
Claims 1, 6-8, 18-19 and 32-34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-21 of U.S. Patent No. 8,485,180 in view of Baker et al (WO 2009152160), Smutney et al (WO 2009152477) and Tarara et al (US 20100272823) as evidenced by Leonard et al (US 20040092470). An obviousness-type double patenting rejection is appropriate because while the conflicting claims are not identical, the examined claims are not patentably distinct from the reference claims because the examined claims would have been obvious over the reference claims in view of Baker et al, Smutney et al and Tarara et al and as evidenced by Leonard et al.
The examined claim 1 is delineated above.
Claim 1 of the ‘180 Patent recites an inhalation system, comprising: a dry powder formulation comprising a plurality of powder particles of a diketopiperazine; and a dry powder inhaler configured to deliver the powder particles to the pulmonary circulation of a subject in a single inhalation and having a container including a cup-like chamber with two relatively flat and parallel sides and a relatively rounded bottom having an internal volume containing the powder particles and a mouthpiece; portions of the inhaler defining a first flow path for 20-70% of the volume of air through the inhaler, said first flow path leading from an inlet to the chamber through the chamber and through at least one outlet from the chamber to the mouthpiece, the inlet and the at least one outlet being configured so that an air flow entering the chamber re-circulates within the internal volume of the chamber tumbling the particles and entraining them in the air flow; the inlet and the at least one outlet further being configured so that the air flow from the inlet is directed across the at least one outlet and controls exit from the chamber of powder particles entrained within the air flow; portions of the inhaler defining a second flow path for 30-80% of the volume of air through the inhaler, said second flow path by-passing the inlet into the chamber and merging with the first path as the first path leaves the at least one outlet; the first flow path changing in direction where it merges with the second flow path, fluidized powder particles exiting the at least one outlet being sheared on contact with the air flow in the second flow path; wherein the inhalation system is configured to deliver the diketopiperazine to the pulmonary circulation of a subject, and said diketopiperazine is measured in a subject's plasma having an AUC greater than 2,300 ng*min/mL per mg of diketopiperazine content in the dry powder formulation.
The differences are that the reference claims do not expressly disclose the active agent being treprostinil, the amount of it, microparticles comprising porous microcrystalline particles or the pore size or specific surface area or the specifics of the inhaler including the cartridge. However, the missing limitations are obvious to one of ordinary skill in the art as taught by Baker et al, Smutney et al and Tarara et al and as evidenced by Leonard et al. Baker et al teach compositions comprising treprostinil and its single dose for inhalation and Tarara et al teach porous microcrystalline cellulose, a pore size of from about 20 nm to about 200 nm and a high porosity (i.e. pore volume) which are suggested for drug delivery to the pulmonary system. Smutney et al also teach a breath-activated dry powder inhalation system comprising a cartridge, wherein the cartridge contains a container (cup) and a lid, and a formulation comprising DKP and an active agent and contain about 20 mg of the said dry powder. As evidenced by Leonard et al, a dry powder formulation contains less than 0.5% water (moisture).
Accordingly, examined claims and reference claims in view of Baker et al, Smutney et al and Tarara et al and as evidenced by Leonard et al are so close that they are not patentably distinct.
Claims 1, 6-8, 18-19 and 32-34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 8,636,001 in view of Baker et al (WO 2009152160) and Tarara et al (US 20100272823) as evidenced by Leonard et al (US 20040092470). An obviousness-type double patenting rejection is appropriate because while the conflicting claims are not identical, the examined claims are not patentably distinct from the reference claims because the examined claims would have been obvious over the reference claims in view of Baker et al and Tarara et al and as evidenced by Leonard et al.
The examined claim 1 is delineated above.
Reference claims recite an inhalation system for delivering a dry powder medicament to a pulmonary tract, comprising a dry powder inhaler configured to have at least two inlet apertures, wherein a first inlet aperture is in communication with a first air flow pathway and a second inlet aperture is in communication with a second air flow pathway, and a container to enclose the dry powder medicament wherein the dry powder medicament comprises diketopiperazine particles. Claim 5 is directed to the inhalation system of claim 3, wherein the cartridge comprises a cartridge top and a cartridge bottom, wherein the cartridge top and the container are configurable to attain a containment position and a dosing or dispensing position.
The differences are that the reference claims do not expressly disclose an active agent or it being treprostinil, the amount of it, microparticles comprising porous microcrystalline particles or the pore size. However, the missing limitations are obvious to one of ordinary skill in the art as taught by Baker et al and Tarara et al and as evidenced by Leonard et al. Baker et al teach compositions comprising treprostinil and its single dose for inhalation and Tarara et al teach porous microcrystalline cellulose, a pore size of from about 20 nm to about 200 nm and a high porosity (i.e. pore volume) which are suggested for drug delivery to the pulmonary system. As evidenced by Leonard et al, a dry powder formulation contains less than 0.5% water (moisture).
Accordingly, examined claims and reference claims in view of Baker et al and Tarara et al as evidenced by Leonard et al are so close that they are not patentably distinct.
Claims 1, 6-8, 18-19 and 32-34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 14, 17-19, 23, 32, 35-38, 49-50 and 53-54 of U.S. Patent No. 8,424,518 in view of Baker et al (WO 2009152160) and Tarara et al (US 20100272823) and as evidenced by Leonard et al. An obviousness-type double patenting rejection is appropriate because while the conflicting claims are not identical, the examined claims are not patentably distinct from the reference claims because the examined claims would have been obvious over the reference claims in view of Baker et al and Tarara et al and as evidenced by Leonard et al.
The examined claim 1 is delineated above.
The reference claims are drawn to a dry powder medicament cartridge for an inhaler, comprising: an enclosure configured to hold a medicament comprising a cartridge top and a cartridge bottom which are moveable relative to one another by a translational motion; at least one inlet port to allow flow into the enclosure, and at least one dispensing port to allow flow out of the enclosure; said at least one inlet port is configured to direct at least a portion of the flow entering the at least one inlet port at the at least one dispensing port within the enclosure in response to a pressure differential. The dry powder comprises an active agent and a diketopiperazine.
The differences are that the reference claims do not expressly disclose an active agent or it being treprostinil, the amount of it, microparticles comprising porous microcrystalline particles or the pore size. However, the missing limitations are obvious to one of ordinary skill in the art as taught by Baker et al and Tarara et al and as evidenced by Leonard et al. Baker et al teach compositions comprising treprostinil and its single dose for inhalation and Tarara et al teach porous microcrystalline cellulose, a pore size of from about 20 nm to about 200 nm and a high porosity (i.e. pore volume) which are suggested for drug delivery to the pulmonary system. As evidenced by Leonard et al, a dry powder formulation contains less than 0.5% water (moisture).
Accordingly, examined claims and reference claims in view of Baker et al and Tarara et al are so close that they are not patentably distinct.
Claims 1, 6-8, 18-19 and 32-34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-7 and 11-13 of U.S. Patent No. 9,662,461 in view of Baker et al (WO 2009152160) and Tarara et al (US 20100272823) and as evidenced by Leonard et al.
An obviousness-type double patenting rejection is appropriate because while the conflicting claims are not identical, the examined claims are not patentably distinct from the reference claims because the examined claims would have been obvious over the reference claims in view of Baker et al and Tarara et al and as evidenced by Leonard et al.
The examined claim 1 is delineated above.
Reference claims recite a dry powder inhaler comprising: at least one rigid air conduit and a housing configured to accept a cartridge, the cartridge comprising a lid and a movable container having a dry powder, the container configured to move relative to the cartridge lid from a storage position to a dispensing position to form a flow path between one or more inlet ports and one or more dispensing ports within the inhaler; and wherein the dry powder inhaler is configured to emit greater than about 75% of a dry powder from the container as powder particles in a single inhalation, and the powder particles emitted have a volumetric median geometric diameter of less than about 5 microns when the single inhalation generates a peak inspiratory pressure of about 2 kPa within two seconds. The container is configured to hold a dry powder medicament and diketopiperazine.
The differences are that the reference claims do not expressly disclose an active agent or it being treprostinil, the amount of it, microparticles comprising porous microcrystalline particles or the pore size. However, the missing limitations are obvious to one of ordinary skill in the art as taught by Baker et al and Tarara et al as evidenced by Leonard et al. Baker et al teach compositions comprising treprostinil and its single dose for inhalation and Tarara et al teach porous microcrystalline cellulose, a pore size of from about 20 nm to about 200 nm and a high porosity (i.e. pore volume) which are suggested for drug delivery to the pulmonary system. As evidenced by Leonard et al, a dry powder formulation contains less than 0.5% water (moisture).
Accordingly, examined claims and reference claims in view of Baker et al and Tarara et al as evidenced by Leonard et al are so close that they are not patentably distinct.
Claims 1, 6-8, 18-19 and 32-34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 8,778,403 in view of Baker et al (WO 2009152160), Smutney et al (WO 2009152477) and Tarara et al (US 20100272823) and as evidenced by Leonard et al (US 20040092470). An obviousness-type double patenting rejection is appropriate because while the conflicting claims are not identical, the examined claims are not patentably distinct from the reference claims because the examined claims would have been obvious over the reference claims in view of Baker et al, Smutney et al and Tarara et al and as evidenced by Leonard et al.
Instant claim 1 is delineated above.
Reference claims recite a method of delivering an active agent to a patient in need thereof and an inhalation system comprising a dry powder comprising microparticles of a diketopiperazine, the microparticles having been loaded with a drug or active agent, by inhalation of said dry powder by said patient. The dry powder is contained in a unit dose cartridge comprising the medicament and diketopiperazine.
The differences are that the reference claims do not expressly disclose the active agent being treprostinil, the amount of it, microparticles comprising porous microcrystalline particles or the pore size or specific surface area or the specifics of the inhaler including the cartridge. However, the missing limitations are obvious to one of ordinary skill in the art as taught by Baker et al, Smutney et al and Tarara et al and as evidenced by Leonard et al. Baker et al teach compositions comprising treprostinil and its single dose for inhalation and Tarara et al teach porous microcrystalline cellulose, a pore size of from about 20 nm to about 200 nm and a high porosity (i.e. pore volume) which are suggested for drug delivery to the pulmonary system. Smutney et al also teach a breath-activated dry powder inhalation system comprising a cartridge, wherein the cartridge contains a container (cup) and a lid, and a formulation comprising DKP and an active agent and contain about 20 mg of the said dry powder. As evidenced by Leonard et al, a dry powder formulation contains less than 0.5% water (moisture).
Accordingly, examined claims and reference claims in view of Baker et al, Smutney et al and Tarara et al and as evidenced by Leonard et al are so close that they are not patentably distinct.
Claims 1, 6-8, 18-19 and 32-34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-27 of U.S. Patent No. 10,201,672 in view of Baker et al (WO 2009152160), Smutney et al (WO 2009152477) and Tarara et al (US 20100272823) as evidenced by Leonard et al (US 20040092470). An obviousness-type double patenting rejection is appropriate because while the conflicting claims are not identical, the examined claims are not patentably distinct from the reference claims because the examined claims would have been obvious over the reference claims in view of Baker et al, Smutney et al and Tarara et al and as evidenced by Leonard et al.
Instant claim 1 is delineated above.
Reference claims recite an inhaler comprising: a housing, a mouthpiece, and a cartridge contained within the housing, the cartridge comprising two or more rigid parts; wherein at least one of the two or more rigid parts of the cartridge is a container, wherein the mouthpiece is configured to translocate the container from a powder containment position in a first location to a dosing position in a second location different than the first location by moving the container relative to another of the at least two or more rigid parts of the cartridge thereby creating an entrance into and an exit from the container when in the dosing position; wherein in the powder containment position, there is not an airflow passageway through the container; and wherein in the dosing position there is an airflow passageway through the container and 10% to 70% of total airflow through the inhaler enters and exits the cartridge. The container is configured to hold a dry powder medicament and diketopiperazine.
The differences are that the reference claims do not expressly disclose the active agent being treprostinil, the amount of it, microparticles comprising porous microcrystalline particles or the pore size or specific surface area or the specifics of the inhaler including the cartridge. However, the missing limitations are obvious to one of ordinary skill in the art as taught by Baker et al, Smutney et al and Tarara et al and as evidenced by Leonard et al. Baker et al teach compositions comprising treprostinil and its single dose for inhalation and Tarara et al teach porous microcrystalline cellulose, a pore size of from about 20 nm to about 200 nm and a high porosity (i.e. pore volume) which are suggested for drug delivery to the pulmonary system. Smutney et al also teach a breath-activated dry powder inhalation system comprising a cartridge, wherein the cartridge contains a container (cup) and a lid, and a formulation comprising DKP and an active agent and contain about 20 mg of the said dry powder. As evidenced by Leonard et al, a dry powder formulation contains less than 0.5% water (moisture).
Accordingly, examined claims and reference claims in view of Baker et al, Smutney et al and Tarara et al and as evidenced by Leonard et al are so close that they are not patentably distinct.
Claims 1, 6-8, 18-19 and 32-34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 17 and 19 of U.S. Patent No. 10,744,280 in view of Baker et al (WO 2009152160), Smutney et al (WO 2009152477) and Tarara et al (US 20100272823) as evidenced by Leonard et al (US 20040092470). An obviousness-type double patenting rejection is appropriate because while the conflicting claims are not identical, the examined claims are not patentably distinct from the reference claims because the examined claims would have been obvious over the reference claims in view of Baker et al, Smutney et al and Tarara et al and as evidenced by Leonard et al.
Instant claim 1 is delineated above.
Reference claims recite a medicament cartridge comprising: a powder container configured to include a location for a dry powder; a lid; and an internal volume, wherein the medicament cartridge is configured to include a containment configuration and a dosing configuration, wherein the lid includes a deflector or stem protruding from an undersurface facing the internal volume, wherein in the dosing configuration the deflector or stem is situated over the location for the dry powder to direct airflow entering the internal volume from a direction parallel to the lid to a substantially downward direction, to a direction substantially parallel to the lid through the location, to a direction substantially perpendicular to the lid to exit the powder container. The powder formulation is delivered via an inhaler and the container is configured to hold a dry powder medicament and diketopiperazine.
The differences are that the reference claims do not expressly disclose the active agent being treprostinil, the amount of it, microparticles comprising porous microcrystalline particles or the pore size or specific surface area or the specifics of the inhaler. However, the missing limitations are obvious to one of ordinary skill in the art as taught by Baker et al, Smutney et al and Tarara et al and as evidenced by Leonard et al. Baker et al teach compositions comprising treprostinil and its single dose for inhalation and Tarara et al teach porous microcrystalline cellulose, a pore size of from about 20 nm to about 200 nm and a high porosity (i.e. pore volume) which are suggested for drug delivery to the pulmonary system. Smutney et al also teach a breath-activated dry powder inhalation system comprising a cartridge, wherein the cartridge contains a container (cup) and a lid, and a formulation comprising DKP and an active agent and contain about 20 mg of the said dry powder. As evidenced by Leonard et al, a dry powder formulation contains less than 0.5% water (moisture).
Accordingly, examined claims and reference claims in view of Baker et al, Smutney et al and Tarara et al and as evidenced by Leonard et al are so close that they are not patentably distinct.
Claims 1, 6-8, 18-19 and 32-34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 10,751,488 in view of Baker et al (WO 2009152160), Smutney et al (WO 2009152477) and Tarara et al (US 20100272823) as evidenced by Leonard et al (US 20040092470). An obviousness-type double patenting rejection is appropriate because while the conflicting claims are not identical, the examined claims are not patentably distinct from the reference claims because the examined claims would have been obvious over the reference claims in view of Baker et al, Smutney et al and Tarara et al and as evidenced by Leonard et al.
Instant claim 1 is delineated above.
Reference claims recite a medicament cartridge for an inhaler, comprising: a cartridge disk including two or more containers configured to hold a medicament; …… . The container is configured to hold a dry powder medicament including a peptide or protein including insulin and diketopiperazine.
The differences are that the reference claims do not expressly disclose the active agent being treprostinil, the amount of it, microparticles comprising porous microcrystalline particles or the pore size or specific surface area or the specifics of the inhaler. However, the missing limitations are obvious to one of ordinary skill in the art as taught by Baker et al, Smutney et al and Tarara et al and as evidenced by Leonard et al. Baker et al teach compositions comprising treprostinil and its single dose for inhalation and Tarara et al teach porous microcrystalline cellulose, a pore size of from about 20 nm to about 200 nm and a high porosity (i.e. pore volume) which are suggested for drug delivery to the pulmonary system. Smutney et al also teach a breath-activated dry powder inhalation system comprising a cartridge, wherein the cartridge contains a container (cup) and a lid, and a formulation comprising DKP and an active agent and contain about 20 mg of the said dry powder. As evidenced by Leonard et al, a dry powder formulation contains less than 0.5% water (moisture).
Accordingly, examined claims and reference claims in view of Baker et al, Smutney et al and Tarara et al and as evidenced by Leonard et al are so close that they are not patentably distinct.
Claims 1, 6-8, 18-19 and 32-34 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 3, 8, 20 and 22-23 of copending Application No. 17/158,997 (US 20210146071) in view of Wilson et al (WO 2014144895), Smutney et al (WO 2009152477), Baker et al (WO 2009152160) and Tarara et al (US 20100272823). An obviousness-type double patenting rejection is appropriate because while the conflicting claims are not identical, the examined claims are not patentably distinct from the reference claims because the examined claims would have been obvious over the reference claims in view of Wilson et al, Smutney et al, Baker et al and Tarara et al.
The examined claims are stated above.
Reference claims are directed to a spray-dried powder composition comprising porous microcrystalline particles of fumaryl diketopiperazine and treprostinil, wherein the treprostinil content is up to about 20% (w/w). Excipients and carriers are claimed.
The differences are that the reference claims do not expressly disclose the pore size or specific surface area. Also, the reference claims disclose the dose in % while the examined claims disclose the dose in µg. However, the missing limitations are obvious to one of ordinary skill in the art as taught by Wilson et al, Baker et al and Tarara et al. Wilson et al teach compositions comprising porous microcrystalline particles of diketopiperazine and wherein the specific surface area is disclosed as less than 67 m2/g and as taught by Tarara et al, a pore size of from about 20 nm to about 200 nm and a high porosity (i.e. pore volume) are suggested for drug delivery to the pulmonary system. Baker et al disclose the administered dose of treprostinil in both percentage and microgram and teach that it could be from 1 to 5000 µg.
Accordingly, examined claims and reference claims in view of references are so close that they are not patentably distinct.
This is a provisional nonstatutory double patenting rejection.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Kinsey et al (WO 2017132601).
Kinsey et al teach a dry powder inhaler including replaceable cartridges containing a dry powder for delivery through the pulmonary tract and lungs, the inhalable dry powders, including medicament formulations comprising active agents for the treatment of diseases such as, pulmonary hypertension, etc, (See abstract).
Disclosed is a dry powder composition comprising microcrystalline particles of fumaryl diketopiperazine and a drug (See [0013] and [0027]).
In some embodiments, the active ingredient comprises treprostinil (See [0015]).
Pulmonary delivery of powders includes carriers and excipients. An exemplary embodiment is fumaryl diketopiperazine, also known as FDKP. DKP crystalline microparticles with a specific surface area (SSA) of between about 35 m2/g and about 67 m2/g exhibit characteristics beneficial to delivery of drugs to the lungs such as improved aerodynamic performance and improved drug adsorption (See [0081]).
Kinsey et al disclose a dry powder for inhalation comprising a plurality of substantially uniform, microcrystalline particles, wherein the microcrystalline particles can be substantially hollow spherical and substantially solid particles comprising crystallites of the diketopiperazine depending on the drug and/or drug content provided and other factors in the process of making the powders. The said microcrystalline particles comprise particles that are relatively porous, having average pore size ranging from about 23 nm to about 30 nm (See [0095]).
In one embodiment, wherein treprostinil is used as the active agent, the dry powder compositions comprise microcrystalline particles of fumaryl diketopiperazine, wherein the treprostinil is adsorbed to the particles and wherein the content of the treprostinil in the composition comprises up to about 20% (w/w) and ranges from about 0.5% to about 10% (w/w), preferably from about 1% to about 5% (w/w) of the dry powder. The said treprostinil composition can be used in the prevention and treatment of pulmonary hypertension by self-administering an effective dose comprising about 1 mg to 15 mg of a dry powder composition comprising microcrystalline particles of fumaryl diketopiperazine and treprostinil in a single inhalation (See [00108]).
Kinsey et al also disclose that the pharmaceutically acceptable carrier for making dry powders can comprise any carriers or excipients useful for making dry powders and which are suitable for pulmonary delivery. Example of suitable carriers and excipients include, sugars, including saccharides and polysaccharides, such as lactose, mannose, sucrose, mannitol, trehalose; citrates, amino acids such as glycine, L-leucine, isoleucine, trileucine, tartrates, zinc citrate, trisodium citrate, polysorbate 80, and the like (See [00110]).
Smutney et al (US 20090308392 or 8,424,518).
Smutney et al teach a breath-powered, dry powder inhaler, a cartridge, and a pulmonary drug delivery system. The inhaler and/or cartridge can be provided with a drug delivery formulation comprising, for example, a diketopiperazine and an active ingredient (See abstract).
It is disclosed that microparticles having a diameter of between about 0.5 and about 10 microns can reach the lungs, successfully passing most of the natural barriers. DKP microparticles with a specific surface area (SSA) of between about 35 and about 67 m2/g exhibit characteristics beneficial to delivery of drugs to the lungs such as improved aerodynamic performance and improved drug adsorption (See [0202]).
Grant et al (US 20140271888).
Grant et al teach diketopiperazine microparticles having a specific surface area of less than about 67 m2/g. The diketopiperazine microparticle can be fumaryl diketopiperazine and can comprise a drug. The said microparticles and methods that allow for improved delivery of drugs to the lungs. Embodiments disclosed herein achieve improved delivery by providing diketopiperazine (DKP) microparticles having a specific surface area (SSA) of between about 35 m2/g and about 62 m2/g. DKP microparticles having a specific surface area in this range exhibit characteristics beneficial to delivery to the lungs such as improved aerodynamic performance and improved drug adsorption (See abstract and [0007]-[0010]).
As specific surface area also affects drug loading/content capacity, various embodiments require specific surface areas greater than or equal to 45 m2/g for improved drug adsorption capacity (See [0048]).
Grant et al disclose a preferred embodiment, in which an inhaler system flow rates ranging from about 7 to 70 liters per minute result in greater than 75% of the container powder content or the cartridge powder content dispensed in fill masses between 1 and 30 mg. The said inhalation system can emit a respirable fraction/fill of a powder dose at greater than 40% in a single inhalation, greater than 50%, greater than 60%, or greater than 70% (See [0012]). In an exemplary embodiment, a respirable fraction on fill can be up to about 80%, wherein about 80% of the fill is emitted with particle sizes <5.8 μm (See [0036]).
It is disclosed that the volumetric median geometric diameter (VMGD) of the various embodiments cartridge emptying of ≧80%, 85%, or 90% and a VMGD of the emitted particles of ≦7.0 μm, or ≦4.8 μm can indicate progressively better aerodynamic performance (See [0035] and Table 4).
Grant et al disclose that the specific surface area of DKP microparticles is a measure of average crystal size and can be used to gauge the relative contributions of crystal nucleation and growth to microparticle characteristics (See [0046]-[0048]).
It is further stated that the combination of a drug and a diketopiperazine can impart improved drug stability and/or absorption characteristics. These microparticles can be administered by various routes of administration. As dry powders these microparticles can be delivered by inhalation to specific areas of the respiratory system, including the lungs (See [0042]).
Such microparticles are self-assembled microparticles and are comprised of aggregated crystalline plates. The stability of the particle can be enhanced by small amounts of a surfactant, such as polysorbate-80 (See [0043]).
Grant et al disclose that “active agent”, used interchangeably with “drug”, refers to pharmaceutical substances, including small molecule pharmaceuticals, macromolecules, biologicals and bioactive agents, including proteins, polypeptides, peptides, vasoactive agents, neuroactive agents, hormones, anticoagulants, immunomodulating agents, cytotoxic agents, antibiotics, antiviral agents, antigens, infectious agents, inflammatory mediators, hormones, etc, (See [0067]).
Response to Arguments
Applicant's arguments filed 05/11/26 have been fully considered but they are not persuasive.
Applicant’s amendments to the claims have necessitated modified grounds of rejections. Applicant’s arguments so far as they pertain to the maintained references and rejections are discussed below.
Applicant’s main argument regarding each of the rejections under 103 as being obvious over the combination of references is that none of the references teach or suggest the added limitation of “residual water content of 0.4%” (See Remarks, pages 7-8).
The above argument is not sufficient to overcome the rejections of record. While none of the previously relied upon expressly disclose the residual water content of the dry powder formulations, Leonard et al teach that a dry powder formulation preferably contains less than 0.5% water. Thus, the added limitation was known and a commonly practiced element of a dry powder formulation.
As such, as we have shown, one of ordinary skill in the art having possession of all the disclosure would have been more than motivated to have made the dry powder as claimed and used with a suitable drug delivery device.
Regarding the second rejection and Roscigno’s teachings Applicant’s only argument is that the reference “fail to cure the deficiencies of the other references, which are discussed above” and that Roscigno “does not disclose any residual water content of the FDKP” (See Remarks, pages 7-8).
The above argument is not found persuasive either. Roscigno et al cures the deficiencies of the other references by teaching that each capsule may contain dosage strengths from 25-300 μg and that each capsule comprises from 0.5 to 1% treprostinil. It is considered that each capsule is a unit dose and a single inhalation. The water content is disclosed by Leonard et al.
Regarding the rejection of claims under obviousness type double patenting, Applicants request for the double patenting rejection of record to be held in abeyance is acknowledged. However, this request to hold a rejection in abeyance is not a proper response to a rejection. Rather, a request to hold a matter in abeyance may only be made in response to an objection or requirements as to form (see MPEP 37 CFR 1.111(b) and 714.02). Accordingly, the rejection will be maintained until a terminal disclaimer is filed or claims are amended to obviate the rejection.
Claims 1, 6-8, 18-19 and 32-34 are rejected. Claims 11-17 are withdrawn.
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 nonprovisional extension fee (37 CFR 1.17(a)) 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Mina Haghighatian whose telephone number is (571)272-0615. The examiner can normally be reached on M-F, 7-5 EST.
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/Mina Haghighatian/
Mina Haghighatian
Primary Examiner
Art Unit 1616
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