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 .
Status of Application
Claims 1-17 are included in the prosecution.
Notice for all US Patent Applications filed on or after March 16, 2013
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 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.
Claims 1-17 are rejected under 35 U.S.C. 103 as being unpatentable over Surber (US 2015/0044288 A1) in view of Miller et al. (US 2004/0025876 A1 – “Miller”).
Instant claim 1 is drawn to a method of preparing an inhalable formulation comprising:
micronizing imatinib particles; and
exposing the micronized imatinib particles to moisture.
Surber teaches a method of preparing formulations of imatinib for aerosolization and use of such formulations for inhaled aerosol administration of imatinib (Abstract). Embodiments include dry powder inhalers (DPI) and metered-dose formulations for therapeutic inhaled delivery of imatinib ([0002], [0021], [0068]-[0070], claims 6-7 and 14-15). A dry powder (DPI) is used to dispense the imatinib or salt thereof, and the fine dry drug particles may be produced by any technique known in the art, including micronization ([0475]). Surber teaches a dry powder imatinib or salt thereof, in a co-crystal/co-precipitate/spray-dried complex or mixture ([0259] and [0314]), a crystalline form of imatinib ([0369]), and a crystalline micronized, dry powder formulation ([0567]).
Surber does not expressly teach exposing the micronized imatinib particles to moisture as recited in instant claim 1 or at least about 1% moisture content as recited in instant claim 14.
Miller teaches dry powder filled capsules for use with dry powder inhalers (DPI) and the it is important to ensure that the water content of the powder does not exceed the critical moisture point, the point at which the powder loses physical and chemical stability (Abstract). The moisture content of the powder can be controlled by utilizing the capsule as a moisture buffer, and by pre-equilibrating the capsule at a pre-determined relative humidity prior to filling minimizes the change in the water content of the powder and ensures that the powder is maintained between its minimum and maximum critical moisture points over an extended period of time ([0012]). The use of a capsule leads to highly efficient delivery of the active agent to the deep lung and increased in-lung pulmonary bioavailability ([0013]). Active agents include imatinib ([0046]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the method of preparing formulations of imatinib for dry powder inhalers and metered-dose formulations for therapeutic inhaled delivery of imatinib, wherein fine dry drug particles are produced by any technique known in the art, including micronization, and wherein a crystalline form of imatinib is used, as taught by Surber, in view of exposure of the inhalable dry powder to a pre-determined relative humidity prior to filling a capsule of the inhalable dry powder, wherein the active agent includes imatinib, as taught by Miller, and produce the instant invention.
One of ordinary skill in the art would have been motivated to do this because Miller teaches that it is important to ensure that the water content of the powder does not exceed the critical moisture point, the point at which the powder loses physical and chemical stability (Abstract), and that the moisture content of the powder can be controlled by utilizing the capsule as a moisture buffer, and by pre-equilibrating the capsule at a pre-determined relative humidity prior to filling minimizes the change in the water content of the powder and ensures that the powder is maintained between its minimum and maximum critical moisture points over an extended period of time ([0012]). Another advantage disclosed by Miller includes the highly efficient delivery of the active agent to the deep lung and increased in-lung pulmonary bioavailability ([0013]).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Regarding instant claim 1, the limitation of a method of preparing an inhalable formulation comprising: micronizing imatinib particles would have been obvious over the fine dry drug particles produced by any technique known in the art, including micronization ([0475]) and the crystalline micronized, dry powder formulation ([0567]), as taught by Surber. The limitation of exposing the micronized imatinib particles to moisture would have been obvious over pre-equilibrating the dry powder filled capsules at a pre-determined relative humidity prior to filling, minimizing the change in the water content of the powder and ensuring that the powder is maintained between its minimum and maximum critical moisture points over an extended period of time ([0012]), as taught by Miller.
Regarding instant claims 2, 3, 4, and 5, the limitations of exposing the micronized imatinib particles to about 50% or more, about 75% or more, about 80% or more, and between about 80% and about 90%, relative humidity at room temperature, respectively, would have been obvious over pre-equilibrating the dry powder filled capsules at a pre-determined relative humidity prior to filling, minimizing the change in the water content of the powder and ensuring that the powder is maintained between its minimum and maximum critical moisture points over an extended period of time ([0012]), as taught by Miller. One of ordinary skill in the art would have found it obvious to use various humidity levels in order to achieve the desired final water content based on the minimum and maximum critical moisture points and to achieve the desired deep lung delivery of the active ingredient ([0013]), as taught by Miller, unless there is evidence of criticality or unexpected results.
Regarding instant claims 6, 7, 8, and 9, the limitations of exposing to moisture for about 1 hour or less, about 2 hours or less, about 3 hours or less, and about 3 hours or more, respectively, would have been obvious over pre-equilibrating the dry powder filled capsules at a pre-determined relative humidity prior to filling ([0012]), as taught by Miller. One of ordinary skill in the art would have found it obvious to expose the micronized particles to moisture for different time periods in order to achieve the desired final water content based on the minimum and maximum critical moisture points and to achieve the desired deep lung delivery of the active ingredient ([0013]), as taught by Miller, unless there is evidence of criticality or unexpected results.
Regarding instant claim 10, the limitation of the exposing step occurring after micronization would have been obvious over the inhalable micronized, dry powder formulation of imatinib ([0002], [0021], [0068]-[0070], claims 6-7 and 14-15, [0475], and [0567]), as taught by Surber, in view of the pre-equilibrating the dry powder (i.e., powder or micronized drug particles) filled capsules at a pre-determined relative humidity prior to filling to minimize the change in the water content of the powder and ensures that the powder is maintained between its minimum and maximum critical moisture points over an extended period of time ([0012]), as taught by Miller.
Regarding instant claim 11, the limitation of filling a capsule with micronized imatinib would have been obvious over the capsule containing the dry powder formulation of imatinib ([0260], [0299], [0476]), as taught by Surber, in view of the dry powder filled capsule (Abstract) and the method of pre-equilibrating the capsule at a pre-determined relative humidity prior to filling minimizes the change in the water content of the powder and ensures that the powder is maintained between its minimum and maximum critical moisture points over an extended period of time ([0012]), wherein active agents include imatinib ([0046]), as taught by Miller.
Regarding instant claim 12, the limitation of the exposing step occurring after filling would have been obvious over exposing the capsule at a pre-determined relative humidity to minimize the change in the water content of the powder and to ensure that the powder is maintained between its minimum and maximum critical moisture points over an extended period of time ([0012]), wherein active agents include imatinib ([0046]), as taught by Miller. One of ordinary skill in the art would have found it obvious to modify the order of exposing the capsule after filling to humidity in order to achieve the desired moisture content, long term stability, delivery of the drug to the deep lung, and optimal pulmonary bioavailability based on the teaching of Miller, unless there is evidence of criticality or unexpected results.
Regarding instant claim 13, the limitation of the inhalable formulation comprising a higher ratio of fine particle dose relative to an equivalent inhalable formulation not subjected to the exposure step would have been an expected result based on the combined teachings of Surber (Abstract, [0002], [0021], [0068]-[0070], claims 6-7 and 14-15, [0475], [0259], [0314], [0369], [0567]) and Miller (Abstract, [0012], [0013], [0046]), absent evidence of criticality or unexpected results.
Regarding instant claims 14-17, the limitations of an inhalable formulation comprising imatinib or a salt thereof would have been obvious over the inhalable formulations of imatinib (Abstract), as taught by Surber, in view of the dry powder filled capsules for use with DPIs (Abstract) wherein the active includes imatinib ([0046]), as taught by Miller. The limitations of at least about 1%, at least about 5%, at least about 10%, and at least about 15% moisture content would have been obvious over the pre-determined relative humidity prior to filling minimizes the change in the water content of the powder and ensures that the powder is maintained between its minimum and maximum critical moisture points over an extended period of time ([0012]), as taught by Miller, absent evidence of criticality or unexpected results.
Conclusion
No claims are allowed.
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/ARADHANA SASAN/Primary Examiner, Art Unit 1615