DETAILED ACTION
Claims 26 and 31-44 is currently pending and under examination.
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 .
Election/Restrictions
Applicant’s election without traverse of Group III in the reply filed on 04/13/2026 is acknowledged.
No claims are withdrawn as a result of the election, as Applicant has canceled all claims corresponding to Groups I and II.
Priority
The instant application is a national stage entry of PCT/US2022/036543, filed 07/08/2022, which claims priority to provisional applications 63/220,362, filed 07/09/2021 and 63/282,356, filed 11/23/2021.
Information Disclosure Statement
Applicant’s Informational Disclosure Statement, filed on 04/02/2024 (2), 05/17/2024, 06/02/2025, 04/13/2026 has been considered. Please refer to Applicant's copy of the 1449 submitted herein.
Claim Objections
Claims 26 and 43 are objected to because of the following informalities:
Claim 26 contains the limitation COPD, an abbreviation, without previously discloses the full term.
Claim 26 contains the limitation “treating a asthma or COPD in a patient”, wherein the use of “a” is grammatically awkward.
Claims 26 and 41 contain the limitation “a plurality of a first species of active agent particles wherein the active agent is budesonide..” and “a plurality of a second species of active agent particles, wherein the active agent albuterol…”. The use of “the active agent” to define the active agent in the first and second particles is unclear as it is defined in two different ways. It would be remedial to clearly link the first active agent to the first particles and second active agent to the second particle. This is further present in claim 41.
Claims 43 contains the term RH, an abbreviation, without previously discloses the full term.
Appropriate correction is required.
Claim Rejections - 35 USC § 112 (b)
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 41 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 41 recites the limitation "the active agents of a reference pharmaceutical composition" in the third line. There is insufficient antecedent basis for this limitation in the claim. There are reference two “active agents” in instant claim 26 defining two different active agents and additional “a reference pharmaceutical composition” does not clearly define the composition to which it is compared. The claims appear to be referencing the pharmaceutical composition of claim 26 wherein the propellant is changed to the HFA-134a, however this is not clearly defined in the instant claims, but will be interpreted as such.
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.
Claim(s) 26, 31-34 and 39-44 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2017/0000725 (IDS dated 04/02/2024) in view of US 2016/0324778 (IDS dated 04/02/2024) and Yang (Understanding Solvation in the Low Global Warming Hydrofluoroolefin HFO-1234ze Propellant, IDS 04/02/2024).
Regarding claim 26, the limitation of a method of treating asthma or COPD in a patient, comprising administering a pharmaceutical composition to the patient by actuating a metered dose inhaler; wherein the metered dose inhaler contains the pharmaceutical composition which comprises a propellant, a plurality of first species of active agents particles comprising budesonide, a plurality of second particles of active agent particles comprising albuterol and a plurality of phospholipid particles comprising perforated microstructures is met by the ‘725 publication teaching compositions of two or more active agents administered via a metered dose inhaler (abstract) wherein the diseases to be treated include asthma and COPD [0046]. Perforated microstructures are taught as suspending particles that include phospholipid ([0063]-[0064]). The composition is taught to include propellants ([0085]-[0088]). Specific active agents are taught to include short acting beta agonists and bronchodilator such as albuterol and corticosteroids including budesonide ([0100], claim 71).
Regarding claims 31-34, the limitation of wherein the budesonide particles are micronized is met by the ‘725 publication teaching budesonide wherein the active agents are in micronized form (claim 71, [0093]). The active agents are taught as present between about 0.05-5 mg/mL [0098]. Corticosteroids such as budesonide is taught to be used in 20 to 200 ug per actuation [0115].
Regarding claims 39-40, the limitation of wherein the phospholipid particles comprise 1,2-Distearoyl-n-glycerol-3-phosphocholidne (DSPC) is met by the ‘725 publication teaches suspending particles are phospholipids DSPC [0175]. The suspending particles are taught to be from 1 mg/ml to 15 mg/ml [0120].
Regarding claims 42-44, the limitation of wherein the metered dose inhaler exhibits less than about 7% reduced shot weight per actuation through the emptying of the canister is met by the ‘725 publication teaching the fine particle dose and delivered dose uniformly characteristics are achieved and substantially maintained through emptying of an MDI [0079]. The DDU is taught to be +/- 20% or better for each of the active agents [0082]. The MDIs were stored valve down at 25 degrees C/60% RH with a foil overwrap. The delivered dose uniformly provided by the said compositions was substantially preserved, even after 12 months storage of such composition at 5 degrees C or after 4.5 months at 25 degrees C and 60% relative humidity. Said composition showed no noticeable degradation in the particle size distribution ([0079]-[0082], [0133], [0179]-[0182]).
The ‘725 publication does not specifically teach the claimed propellant having a purity of about 99.95% or higher (claim 26).
The ‘778 publication teach medicinal compositions, and devices, methods and systems which use same, comprising a propellant and at least one medicinally active compound, said propellant comprising at least one fluoroolefin (See Abstract). The ‘778 publication disclose that “Thus, applicants have recognized a need for compounds, compositions, systems, devices and methods for medicament delivery that at once provide relatively low ozone depletion potential and relatively low global warming potential. Moreover, applicants have recognized that any composition, including any propellant contained therein, must also possess properties which ensure the efficacy of the medicament, such as medicament stability, low- or no-toxicity, and compatibility with the other components of the medicament delivery system” (See [0012]). The said fluoroolefin comprises tetrafluoropropene, more preferably 1,1,1,3-tetrafluoropropene (HFO-1234ze) and/or 1,1,1,2-tetrafluoropropene (HFO-1234yf). The term HFO-1234ze is used herein generically to refer to 1,1,1,3-tetrafluoropropene, independent of whether it is the cis- or trans-form. The terms “cisHFO-1234ze” and “transHFO-1234ze” are used herein to describe the cis- and trans-forms of 1,1,1,3-tetrafluoropropene respectively (See [0014]). It is disclosed that the said propellants have the advantage of not contributing substantially to ozone depletion or global warming compared to hydrofluoroalkanes, which are commonly used (See [0016]). The ‘778 publication teach that the said compositions comprise at least about 50% by weight, and even more preferably from about 60% to about 99%, or more, by weight, of propellant based upon the total weight of the composition, and from about 0.01% to about 0.5% by weight of medicinally active compounds (See [0021]). Particularly preferred medicinal agents for use in the said compositions include bronchodilators and anti-inflammatory steroids for use in the treatment of respiratory disorders, such as asthma and chronic obstructive pulmonary disorder (COPD), by inhalation therapy (See [0026]). Exemplary medicaments may be selected from, budesonide, mometasone furoate, formoterol and an anticholinergic (See [0027]). It is disclosed that HFO-1234ze comprises a combination of transHFO-1234ze and cisHFO-1234ze, and more preferably from about 90% to about 99% trans on the basis of total HFO-1234ze, with the cis isomer comprising from about 1% to about 10% of the same basis. The said propellant compositions comprise a combination of cisHFO-1234ze and transHFO1234ze, preferably in a cis:trans weight ratio of from about 1:99 to about 10:99, more preferably from about 1:99 to about 5:95. It is disclosed that transHFO-1234ze may be preferred for use in certain systems because of its relatively low boiling point (−19° C.) (See [0036]-[0037]).
Yang teaches that hydrofluoroolefins (HFOs), with zero ozone-depleting effect and very low global warming potential, are considered to be the next-generation high-pressure working fluids. They have industrial relevance in areas including refrigeration and medical aerosols. One major challenge expected in the replacement of existing working fluids with HFOs is the solubility and solvation of additives in such hydrophobic and oleophobic low dielectric semifluorinated solvents. The study of the solvation of chemistries that represent those additives by HFOs is, therefore, of great relevance.
Yang et al teach that they systematically investigate how the polarity and structure of fragments (the tail, t) that represent those additives affect their binding energy (Eb) with HFO-1234ze (1,1,1,3-tetrafluoropropene). We also compare and contrast those results with those for the working fluids that are most widely used in the industry, the hydrofluoroalkanes (HFAs) HFA-134a and HFA-227. Three main chemistries were investigated: alkanes, ethers, and esters. It was found that HFO-1234ze interacts quite favorably with ethers and esters, as indicated by their Eb st, while Eb st with alkanes was much lower. While ether and ester groups showed little difference in Eb st, the much lower self-interaction energy between ether tail−tail fragments (Eb tt) is expected to result in improved solubility/solvation of those groups in HFO-1234ze when compared with the more polar ester groups. The ratio Eb st/Eb tt is defined as the enhancement factor (Eenh) and is expected to be a better predictor of solubility/solvation of the tail fragments. Finally, the solvation behavior of HFO-1234ze was found to be similar to that of HFA-134a, thus suggesting similar considerations may apply for both propellants, when solvation properties are of a concern to the application (See abstract).
In Table 1, Yang et al disclose some relevant physicochemical properties of the fourth-generation propellant HFO-1234ze compared with the hydrofluoroalkanes HFA-134a and HFA227. It is stated that within this context, hydrofluoroolefins (HFOs) have emerged as the fourth-generation propellants. HFOs have no ODE and very low GWP. HFO-1234ze (1,1,1,3-tetrafluoropropene), one of the HFO candidates, has been shown to be nonflammable, to have low toxicity (similar to that of HFAs), and to possess physicochemical properties similar to HFAs. These characteristics are expected to somewhat facilitate the transition process from HFAs to HFOs (See page 10676, 1st col.).
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use HFR-1234ze as taught by the ‘778 publication in the composition taught by the ‘725 publication because the ‘778 publication teaches that HFO-1234ze is a better propellant because, at least, it is advantageous in not contributing to ozone depletion and global warming. One of ordinary skill in the art before the filing date of the claimed invention would have a reasonable expectation of success as the ‘778 publication and the ‘725 publication are both directed to compositions comprising propellants, budesonide and albuterol to treat COPD, thus teaching overlapping ingredients and providing an expectation of success in using the propellant taught by the ‘778 publication in the composition of the ‘725 publication. One of ordinary skill in the art before the filing date of the claimed invention would be motivated to use HFO-1234ze as the propellant in the composition of the ‘725 publication because Yang et al teach that HFO propellants, and especially HFO-1234ze is a suitable alternative to HFA propellants because of at least, their lower impact on the environment. In other words, in view of the teachings of the ‘725 publication, the ‘778 publication and Yang, there would have been a reasonable expectation that a composition comprising HFO-1234ze and pharmaceutically active agents including corticosteroids such as budesonide and albuterol could be successfully prepared and used in a method for treating pulmonary diseases such as asthma and COPD.
Regarding the limitations of comparable or better bioavailability of the claimed compositions (Claims 41-44), it is noted that the claimed limitations are considered a result achieved by the claimed method and composition. That is, it would have been expected that one of ordinary skill in the art following the teachings of the ‘725 publication and the ‘778 publication, arriving at the same composition and method as claimed would have achieved the same results.
Claim(s) 35-38 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2017/0000725 in view of US 2016/0324778 and Yang as applied to claims 26, 31-34 and 39-44 above, and further in view of US 2003/0140920.
As mentioned in the above 103 rejection, all the limitations of claims 26, 31-34 and 39-44 are taught by the combination of the ‘725 publication, the ‘778 publication and Yang.
Regarding claims 36-38, the ‘725 publication teaching the active agents are in micronized form (claim 71, [0093]). The active agents are taught as present between about 0.05-5 mg/mL [0098]. Active agents are taught to be used in 20 to 200 ug per actuation [0115]. That being said and in lieu of objective evidence of unexpected results, the dosage can be viewed as a variable which achieves the recognized result of successfully treating a specific patient. The optimum or workable range of dosing can be accordingly characterized as routine optimization and experimentation (see MPEP 2144.05 (II)B). “[Discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” In re Boesch, 617 F.2d 272, 276 (CCPA 1980). Applicants provide no evidence of any secondary consideration such as unexpected results that would render the optimized amounts of dosage nonobvious.
The combination of references does not specifically teach albuterol sulfate (claims 35-36).
The ‘920 publication teaches the preferred salt of albuterol is sulfate and is used for inhalation ([0022]-[0025]) and is used to treat asthma (abstract).
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use albuterol sulfate for the albuterol taught by the ‘725 publication because the ‘725 publication teaches the use of albuterol wherein the active agents may be used in salt forms and the ‘920 publication teaches albuterol sulfate to be the preferred salt form of albuterol, thus providing a motivation and expectation of success in using the specific albuterol sulfate taught to treat asthmas in the composition containing albuterol taught to treat asthma.
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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 26, 31-32 and 39-44 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 9-11, 13-16, 19-22 and 25-28 of copending Application No. 18/577,165 in view of US 2017/0000725. The ‘165 application teaches a compristion delivered via an inhaler comprising HFO-1234ze€ having a purity of at least 99.90%, a plurality of one or more active gent particles and a plurality of phospholipid particles comprising a perforated microstructures wherein the active agent is micronized and provides the desired Cmax DDU and is used to treat asthma and COPD. The instant claims differ in that they also include albuterol. The ‘725 publication teaching compositions of two or more active agents administered via a metered dose inhaler (abstract) wherein the diseases to be treated include asthma and COPD [0046]. Perforated microstructures are taught as suspending particles that include phospholipid ([0063]-[0064]). The composition is taught to include propellants ([0085]-[0088]). Specific active agents are taught to include short acting beta agonists and bronchodilator such as albuterol and corticosteroids including budesonide ([0100], claim 71). It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to include albuterol in the composition taught by the 165 application as both the ‘165 application and the ‘725 publication are compositions comprising propellant, budesonide and phospholipid particles to treat asthma and the ‘725 publication additionally comprises a second active ingredient selected form a group including albuterol, thus providing motivation to use the combination of active agents to treat asthma or COPD.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNDSEY MARIE BECKHARDT whose telephone number is (571)270-7676. The examiner can normally be reached Monday-Thursday 9am to 4pm and Friday 9am to 2pm.
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/LYNDSEY M BECKHARDT/Examiner, Art Unit 1613
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