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 .
Claims 1-12, 14-15 and 17-21 have been presented for examination on the merits.
Priority
This Application is a continuation of Application No. 17/280,452 filed on 03/26/2021 which is a 371 of PCT/GB2019052863 filed on 10/09/2019 which claims benefit to Application No. 1816447.5 filed in United Kingdom on 10/09/2018.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 12 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 12 is indefinite because it ends with -comprising-. It appears that the claim is incomplete. Accordingly, the claim is indefinite.
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.
Applicant’s claim
Claim 1 is the broadest claim and is drawn to a method of treating chronic obstructive pulmonary disease (COPD) or asthma in a subject, which method comprises administering to said subject an effective amount of a liquid pharmaceutical composition, which liquid pharmaceutical composition is suitable for administration by inhalation and comprises (i) a suspension of particles comprising 9,10-dimethoxy-2-(2,4,6- trimethylphenylimino)-3 -(N-carbamoyl-2-aminoethyl)-3 ,4,6,7-tetrahydro-2H-pyrimido [6,1 - a]isoquinolin-4-one (RPL554); and (ii) a diluent which is 1,1,1 ,2-tetrafluoroethane (HFA- 134a), wherein the liquid pharmaceutical composition comprises less than 0.05 % by weight of a surfactant relative to the total weight of the composition.
Claims 1-12, 14-15 and 17-21 are rejected under 35 U.S.C. 103 as being unpatentable over Abbott-Banner et al (US 20170112839).
Abbott-Banner et al teach a compound and a composition used in a method of treating a disease or condition selected from chronic obstructive pulmonary disease (COPD), asthma, mild pulmonary disease, cystic fibrosis, bronchitis, bronchiectasis, etc, which compound is 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one (RPL554) or a pharmaceutically acceptable acid addition salt thereof (See abstract, [0004], [0008]-[0011] and claim 12).
Regarding claim 1, Abbott-Banner et al state that the active agent can be micronized and combined with a suitable carrier to form a suspension of micronized particles of respirable size, and wherein the composition may comprise 0% surfactant. The said suspension of the active agent is in a liquefied propellant, such as 1,1,1,2-tetrafluoroethane (HFA 134a) (See [0059] and [0062]).
Regarding claims 2-8 and 17-20, Abbott-Banner et al teach metered-dose formulations typically comprise a solution or suspension of the active agent in a liquefied propellant, with other optional components. A representative composition for use in an MDI comprises from about 0.01-5 wt % of active agent; from about 0-20 wt % ethanol; and from about 0-5 wt % surfactant; with the remainder being an HFA propellant (See [0062]).
Regarding claim 9, Abbott-Banner et al teach a suspension of micronized particles of respirable size, and where micronized is typically defined as having particles in which at least about 90 percent of the particles have a mass median diameter of less than about 10 μm (See [0059]).
Regarding claim 10, Abbott-Banner et al teach an isotonic aqueous solution comprising from about 0.05 μg/mL to about 10 mg/mL of RPL554 (See [0060]).
Regarding claims 11-12, Abbott-Banner et al teach that the said pharmaceutical compositions are suitable for inhaled administration. The pharmaceutical composition may be for administration by nebulizer, dry powder inhaler (DPI) or metered-dose inhaler (MDI) (See [0057]).
Regarding claims 14-15, Abbott-Banner et al teach that the disease or condition may be cystic fibrosis, chronic obstructive pulmonary disease (COPD), mild asthma, severe asthma, mild pulmonary disease, chronic bronchitis, etc, (See [0040]).
Regarding claim 20, Abbott-Banner et al also teach that the composition will contain from about 0.01-95 wt % of active agent (See [0054]).
Regarding claim 21, Abbott-Banner et al teach that the amount of RPL554 present in a single dose may be from 1 μg to 50 mg. The dose of RPL554 may be from 1 μg/kg to 500 μg/kg, or from 50 μg/kg to 250 μg/kg (kg as weight of patient). A dose may be administered as often as required, such as twice daily, once daily, etc, (See [0072]).
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 followed the teachings of Abbott-Banner et al to arrive at the instant invention with reasonable expectation of success.
One of ordinary skill in the art would have been motivated to follow Abbott-Banner et al’s teachings and method to make a composition consisting of RPL554 and HFA propellant for inhalation by a metered dose inhaler to treat asthma and COPD because Abbott-Banner et al teach the said composition as one of the embodiments of their disclosure and that it is effective in treating respiratory disorders including asthma and COPD.
In other words, Abbott-Banner et al disclose an embodiment where the composition consists of RPL554 and an HFA propellant.
The claims would have been obvious because a person of ordinary skill has good reasons to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
Regarding claim 6, Abbott-Banner et al teach embodiments wherein the active agent is solely RPL554. Regarding claim 21, while Abbott-Banner et al do not expressly disclose a delivered dose per actuation, they disclose the amount of the medicament delivered per dose and it is delivered by a metered dose inhaler. Accordingly, one of ordinary skill in the art would have recognized that a single dose can be per actuation.
Claims 1-12, 14-15 and 17-21 are rejected under 35 U.S.C. 103 as being unpatentable over Akehurst et al (WO 1993011744) in combination with Spargo et al (US 20170239178).
Akehurst et al teach aerosol formulations of use for the administration of medicaments by inhalation, in particular a pharmaceutical aerosol formulation which comprises particulate medicament and a propellant, which formulation is substantially free of surfactant and a method of treating respiratory disorders which comprises administration by inhalation of an effective amount of the said pharmaceutical aerosol formulation (See abstract).
Regarding claims 1-5, 7-8 and 17-20 in part, Akehurst et al disclose a pharmaceutical aerosol medicament which comprises particulate medicament and a propellant, and wherein the said propellant is 1,1, 1,2-tetrafluoroethane (HFA 134a). it is disclosed that they have surprisingly found that, it is in fact possible to obtain satisfactory dispersions of medicaments in fluorocarbon or hydrogen-containing chlorofluorocarbon propellants such as 1,1, 1,2-tetrafluoroethane (HFA 134a) without recourse to the use of any surfactant or cosolvent in the composition, or the necessity to pre-treat the medicament prior to dispersal in the propellant. The term "substantially free" is defined as less than 1% w/w based upon the fluorocarbon or hydrogen-containing chlorofluorocarbon, in particular less than 0.5% for example 0.1% or less (See Page 2, lines 12-16 and 22-24 and claims 1-3). The particulate medicament is added to a charge vessel and liquified propellant is pressure filled through the charge vessel into a manufacturing vessel. The drug suspension is mixed before recirculation to a filling machine and an aliquot of the drug suspension is then filled through the metering valve into the canister (See page 8, lines 12-15). Akehurst et al also disclose that “medicaments which may be administered in aerosol formulations according to the invention include any drug useful in inhalation therapy which may be presented in a form which is substantially completely insoluble in the selected propellant”. Particularly preferred medicaments for administration using the said aerosol formulations include anti-allergies, bronchodilators and anti-inflammatory steroids of use in the treatment of respiratory disorders such as asthma by inhalation therapy (See Page 2, line 29 to Page 3, line 25).
Regarding claim 9, in part, Akehurst et al disclose that the particle size of the particulate (e.g. micronised) medicament should be such as to permit inhalation of substantially all of the medicament into the lungs upon administration of the aerosol formulation and will thus be in the range 1-10 microns, e.g. 1-5 microns (See Page 2, lines 25-28).
Regarding claims 1-5, 7-8 and 17-20 in part, Akehurst et al further disclose a particularly preferred embodiment provides a pharmaceutical aerosol formulation consisting essentially of one or more particulate medicament and one or more propellant (See page 5, lines 21-25). The final aerosol formulation desirably contains 0.005-10% w/w of medicament relative to the total weight of the formulation (See Page 4, lines 16-18).
Regarding claims 11-12 and 21 in part, Akehurst et al teach that metered dose inhalers are designed to deliver a fixed unit dosage of medicament per actuation or "puff", for example in the range of 10 to 5000 microgram medicament per puff (See page 8, lines 24-26). In Example 3, Akehurst et al disclose that micronised terbutaline sulphate (60mg) is weighed directly into an aluminium can and 1, 1, 1,2-tetrafluorethane (to 18.2g) added from a vacuum flask. A metering valve is crimped into place and the sealed can sonicated for five minutes. The aerosol delivers 250 microgram terbutaline sulphate per actuation.
Akehurst et al lack a specific disclosure on the medicament being RPL554 or its concentration. However, these are known in the art as shown by Spargo et al.
Spargo et al teach a liquid pharmaceutical composition suitable for administration by inhalation which comprises a diluent and a suspension of particles of 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl-)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one (RPL554) or a pharmaceutically acceptable salt thereof for use in the treatment of a human or animal (See abstract). Regarding claims 1, 6 and 10, Spargo et al teach that the concentration of particles of RPL554 in the liquid pharmaceutical composition is typically from about 0.01 mg/mL to about 40 mg/mL (See [0031] and claim 1).
Regarding claim 9, Spargo et al teach that the particles of RPL554 may be of any suitable size for a use in a liquid pharmaceutical composition suitable for inhalation, and may have a Dv50 (median particle size by volume) of from about 0.1µm to about 8 µm and particularly from about 0.2 µm to about 5 µm (See [0015]-[0016] and claim 2).
Regarding claims 1, 14-15 and 20-21, Spargo et al teach that the said liquid pharmaceutical composition may be used in the treatment of a disease or condition selected from asthma, allergic asthma, chronic obstructive pulmonary disease (COPD), etc. Typically, said disease or condition is asthma, severe asthma, steroid resistant asthma, pediatric asthma, or COPD, more typically COPD. The said method of treating comprises administering to said subject an effective amount of the said liquid pharmaceutical composition (See [0009]-[0011] and [0062]). A single dose of RPL554 may be from 0.5 mg to 6 mg, for instance about 1.5 mg. Doses may be administered once, twice or three times daily. For instance, the dose of RPL554 may be from 0.1 mg/day to 50 mg/day, typically from 1.5 mg/day to 18 mg/day. These doses are typically the nominal dose emitted from the inhaler (See [0064]).
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 Spargo et al with that of Akehurst et al to arrive at the instant invention.
One of ordinary skill in the art would have been motivated to do so because Akehurst et al teach a method of treating a respiratory disorder such as asthma by administration of a composition comprising an active agent and an HFA propellant via a metered dose inhaler. Akehurst et al teach that they have surprisingly found that, it is in fact possible to obtain satisfactory dispersions of medicaments in a propellant such as 1,1, 1,2-tetrafluoroethane (HFA 134a) without recourse to the use of any surfactant or cosolvent in the composition. Akehurst et al do not expressly disclose the medicament being RPL554. However as taught by Spargo et al, RPL554 is a known medicament that is effectively administered to subjects in need of a respiratory treatment such as asthma, allergic asthma, pediatric asthma or COPD via a metered dose inhaler.
Accordingly, one of ordinary skill in the art would have been motivated to have incorporated Spargo et al’s active agent, RPL554, into the surfactant free, co-solvent free compositions of Akehurst et al with a reasonable expectation of success.
The claims would have been obvious because the substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention.
Additionally, the claims would have been obvious because a person of ordinary skill has good reasons to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
Claims 1-12, 14-15 and 17-21 are rejected under 35 U.S.C. 103 as being unpatentable over Akehurst et al (WO 1993011744) in view of Walker et al (WO 2014140648 relying on recitations form US 20170266190).
Akehurst et al’s teachings are delineated above and incorporated herein.
Akehurst et al lack a specific disclosure on the medicament being RPL554 or its concentration. However, these are known in the art as shown by Walker et al.
Walker et al teach a composition which comprises (a) a PDE3/PDE4 inhibitor which is 9,10-Dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one (RPL554) or a pharmaceutically acceptable acid addition salt thereof and (b) a muscarinic receptor antagonist. The free base of RPL554 is preferred (See abstract and [0047]).
Disclosed is also a method of treating a disease or condition which is based on (i) acute or chronic obstruction of bronchi or (ii) acute or chronic inflammation, in a subject in need thereof, which method comprises administering to said subject (a) a PDE3/PDE4 inhibitor and (b) a muscarinic receptor antagonist (See [0013]).
The said composition suitable for inhalation will contain from about 0.01-95 wt % of active agent, including, from about 0.01-30 wt %, such as from about 0.01-10 wt % (See [0062]).
In exemplary composition for use in a nebulizer inhaler comprises an isotonic aqueous solution comprising from about 0.05 μg/mL to about 10 mg/mL of a RPL554 (See [0068]).
Metered-dose formulations typically comprise a solution or suspension of the active agent in a liquefied propellant, such as 1,1,1,2-tetrafluoroethane (HFA 134a). A representative composition for use in an MDI comprises from about 0.01-5 wt % of active agent; from about 0-20 wt % ethanol; and from about 0-5 wt % surfactant; with the remainder being an HFA propellant (See [0069]).
Walker et al discloses that the disease or condition is asthma, allergic asthma, chronic obstructive pulmonary disease (COPD), severe asthma, pediatric asthma, cystic fibrosis, etc, and preferably, the condition is asthma or chronic obstructive pulmonary disease (COPD) (See [0045] and claims 10-11).
Walker et al disclose that typically, the said compositions are useful for treating pulmonary or respiratory disorders, such as COPD or asthma, in mammals including humans, by administering to a patient a therapeutically effective amount of the composition. Generally, the dose for treating a pulmonary disorder will range from about 10-1500 μg/day. (See [0106]-[0108]).
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 Walker et al with that of Akehurst et al to arrive at the instant invention.
One of ordinary skill in the art would have been motivated to do so because Akehurst et al teach a method of treating a respiratory disorder such as COPD by administration of a composition comprising and active agent and an HFA propellant via a metered dose inhaler. Akehurst et al teach that they have surprisingly found that, it is in fact possible to obtain satisfactory dispersions of medicaments in a propellant such as 1,1, 1,2-tetrafluoroethane (HFA 134a) without recourse to the use of any surfactant or cosolvent in the composition. Akehurst et al do not expressly disclose the medicament being RPL554. However as taught by Walker et al, RPL554 is a known medicament that is effectively administered to subjects in need of a respiratory treatment such as asthma and COPD via a metered dose inhaler.
Accordingly, one of ordinary skill in the art would have been motivated to have incorporated Walker et al’s active agent, RPL554, into the surfactant free, co-solvent free compositions of Akehurst et al with a reasonable expectation of success.
The claims would have been obvious because the substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention.
Additionally, the claims would have been obvious because a person of ordinary skill has good reasons to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
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 1-12, 14-15 and 17-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 and 17-18 of U.S. Patent No. 9,956,171 in view of Akehurst et al (WO 1993011744). 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 Akehurst et al.
Specifically, the examined claim 1 is delineated above.
The reference claims are drawn to a liquid pharmaceutical composition suitable for administration by inhalation comprising a diluent and a suspension of particles of 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one (RPL554) or a pharmaceutically acceptable salt thereof, wherein the particles of RPL554 have a particle size distribution with a Dv50 (median particle size by volume) value of from about 0.2 μm to about 5 μm. And a method of treating a disease or condition selected from asthma, allergic asthma, hay fever, allergic rhinitis, bronchitis, emphysema, bronchiectasis, chronic obstructive pulmonary disease (COPD), ….. in a subject, which method comprises administering to said subject an effective amount of a liquid pharmaceutical composition according to claim 1.
The differences include 1- the examined claims are drawn to a method of treating a respiratory disorder, while the reference claims are drawn to both a liquid pharmaceutical composition and a method of treating a respiratory disorder. This is however obvious because the said liquid formulation is necessary to achieve the claimed method. 2- the reference claims do not recite that the diluent is an HFA propellant and 3- the reference claims do not recite the amount of surfactant is less than 0.05 wt% or the dose per actuation. However, in view of Akehurst et al, these modifications would have been obvious because Akehurst et al also teach a method of treating respiratory disorders such as asthma and COPD comprising administration of a composition comprising an active agent, an HFA propellant and substantially no surfactant and co-solvent. Akehurst et al also provide guidance on the actuated dose of an active agent. As such one of ordinary skill in the art would have been motivated to include a propellant and exclude a surfactant and a co-solvent/excipient in the formulation for preparing the disclosed successful compositions and methods.
Claims 1-12, 14-15 and 17-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-4, 6-7, 10-12 of U.S. Patent No. 10,463,665 in view of Akehurst et al (WO 1993011744). 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 Akehurst et al.
The examined claim 1 is delineated above and incorporated herein.
The reference claims are drawn to a pharmaceutically acceptable acid addition salt of: (i) 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one (RPL554); and (ii) ethane-1,2-disulfonic acid. And a method of treating a disease or condition selected from asthma, allergic asthma, hay fever, allergic rhinitis, bronchitis, emphysema, bronchiectasis, chronic obstructive pulmonary disease (COPD), ….. in a subject, which method comprises administering to said subject an effective amount of a liquid pharmaceutical composition according to claim 1.
The differences include 1- the examined claims are drawn to a method of treating a respiratory disorder, while the reference claims are drawn to both a pharmaceutical composition and a method of treating a respiratory disorder. This is however obvious because the said liquid formulation is necessary to achieve the claimed method. 2- the reference claims do not recite that the diluent is an HFA propellant and 3- the reference claims do not recite the amount of surfactant is less than 0.05 wt% or the dose per actuation. However, in view of Akehurst et al, these modifications would have been obvious because Akehurst et al also teach a method of treating respiratory disorders such as asthma and COPD comprising administration of a composition comprising an active agent, an HFA propellant and substantially no surfactant and co-solvent. Akehurst et al also provide guidance on the actuated dose of an active agent. As such one of ordinary skill in the art would have been motivated to include a propellant and exclude a surfactant and a co-solvent/excipient in the formulation for preparing the disclosed successful compositions and methods.
Claims 1-12, 14-15 and 17-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 10,945,950 in view of Akehurst et al (WO 1993011744). 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 Akehurst et al.
The examined claim 1 is delineated above and incorporated herein.
The reference claims are drawn to a liquid pharmaceutical composition suitable for administration by inhalation comprising a diluent and a suspension of particles of 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one (RPL554) or a pharmaceutically acceptable salt thereof, wherein the composition comprises a phosphate buffer at a concentration of less than about 5 mg/mL; wherein the particles of RPL554 have a particle size distribution with a Dv50 (median particle size by volume) value of from about 0.2 μm to about 5 μm, wherein the concentration of particles of RPL554 in the liquid pharmaceutical composition is from about 0.1 mg/mL to about 6 mg/mL.
The differences include 1- the examined claims are drawn to a method of treating a respiratory disorder, while the reference claims are drawn to both a pharmaceutical composition and a method of treating a respiratory disorder. This is however obvious because the said liquid formulation is necessary to achieve the claimed method. 2- the reference claims do not recite that the diluent is an HFA propellant and 3- the reference claims do not recite the amount of surfactant is less than 0.05 wt% or the dose per actuation. However, in view of Akehurst et al, these modifications would have been obvious because Akehurst et al also teach a method of treating respiratory disorders such as asthma and COPD comprising administration of a composition comprising an active agent, an HFA propellant and substantially no surfactant and co-solvent. Akehurst et al also provide guidance on the actuated dose of an active agent. As such one of ordinary skill in the art would have been motivated to include a propellant and exclude a surfactant and a co-solvent/excipient in the formulation for preparing the disclosed successful compositions and methods.
Claims 1-12, 14-15 and 17-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 15-16 of U.S. Patent No. 11,491,155 in view of Akehurst et al (WO 1993011744) and Walker et al (US 20170266190). 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 Akehurst et al and Walker et al.
The examined claim 1 is delineated above and incorporated herein.
The reference claims are drawn to pharmaceutically acceptable acid addition salt of: (i) 9,10-dimethoxy-2-(2,4,6-trimethyl phenylimino)-3-(N-carbamoyl-2-aminoethyl)- 3,4,6,7-tetrahydro-2H-pyrimido[6, l-a]isoquinolin-4-one (RPL554); and (ii) ethanesulfonic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, hydrobromic acid or sulfuric acid, or a solvate thereof, a pharmaceutical composition comprising the said compound and a method of treating a respiratory disorder by administration of the said composition to the subject
The differences include 1- the examined claims are drawn to a method of treating a respiratory disorder, while the reference claims are drawn to an acid addition, a pharmaceutical composition and a method of treating respiratory disorder. This is however obvious because the said liquid formulation is necessary to achieve the claimed method. 2- the reference claims are drawn to an acid addition of RPL554 while examined claims are drawn to a method of treating a disease or condition such as asthma or COPD by administration of the said compound. However, as recited by Walker et al, the composition may comprise the free base or acid addition of RPL554. 3- the reference claims do not recite the amount of surfactant is less than 0.05 wt% or the dose per actuation. However, in view of Akehurst et al, these modifications would have been obvious because Akehurst et al also teach a method of treating respiratory disorders such as asthma and COPD comprising administration of a composition comprising an active agent, an HFA propellant and substantially no surfactant and co-solvent. Akehurst et al also provide guidance on the actuated dose of an active agent. As such one of ordinary skill in the art would have been motivated to include a propellant and exclude a surfactant and a co-solvent/excipient in the formulation for preparing the disclosed successful compositions and methods. Both Akehurst and Walker provide guidance on the dose per actuation of an active agent including RPL554. As such one of ordinary skill in the art would have been motivated to include a propellant and exclude a surfactant and a co-solvent/excipient in the formulation for preparing the disclosed successful compositions and methods.
Claims 1-12, 14-15 and 17-21 are rejected.
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 M-F, 7-5 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sue X. Liu can be reached on 571-272-5539. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Mina Haghighatian/
Mina Haghighatian
Primary Examiner
Art Unit 1616