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 the Application
Claims 1-12 are pending
Claims 1-12 are under consideration in the instant office action.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 05/31/2024, 12/11/2024, 04/02/2025, 04/22/2025 complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, it has been placed in the application file and the information therein has been considered as to the merits. See attached copy of the PTO-1449.
Priority
This application claims benefit of U.S. Provisional Application No. 62/208,134 filed on 06/08/2021 and U.S. Application No. 17/832,210 filed on 06/03/2022.
Claim Rejections - 35 USC § 103
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.
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.
Claims 1-6, 8, and 10-12 are rejected under 35 U.S.C. 103 as being unpatentable over Lorbek et al. (WO 2020/127819, as disclosed in IDS) in view of Ahmed et al. (US 10,709,662, as disclosed in IDS).
Rejection
Lorbek et al. teaches “Apixaban is a factor Xa inhibitor and can be used for the treatment or prevention of a thromboembolic disorder.” (pg. 1, lines 15-16). Lorbek et al. teaches “The pharmaceutical composition of the present invention is preferably formulated in a unit 10 dosage form, each unit dosage form containing about 1 to about 100 mg of apixaban, more preferably about 2 to about 8 mg of apixaban, most preferably 2.5 mg or 5 mg. The term "apixaban" can relate to apixaban in crystalline form,” (pg. 28, lines 9-14). Lorbek et al. teaches the composition formulated for immediate release (pg. 16, lines 6-11).
Lorbek et al. does not teach a film comprising apixaban.
Ahmed et al. is drawn towards mucoadhesive buccal films (see abstract). Ahmed et al. teaches such films comprising inclusion complexes useful for the insertion of a hydrophobic drug into the cavity of a hydrophilic polymer (col. 2, lines 39-54). Ahmed et al. teaches oral dissolving films that can dissolve within 30 seconds, which can comprise bioadhesive polymers such as hydroxypropyl methyl cellulose in an amount of 1-10% (col. 4, lines 17-53). Ahmed et al. teaches polyethylene glycols as a suitable plasticizer (col. 5, lines 15-17). Ahmed et al. teaches formulating compositions with the remaining component being water (col. 3, lines 37-41). Ahmed teaches “The films described herein may be any desired thickness and size such that it may be placed into the oral cavity of the user. For example, the films may have a relatively thin thickness of from about 1 to about 300 μm, or they may have a somewhat thicker thickness of from about 300 to about 800 μm.” (col. 4, lines 7-14).
It would have been obvious to one of ordinary skill in the art to formulate a film of apixaban, as suggested by Ahmed et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to do so since such films allow for improved bioavailability and delivery of poorly soluble drugs as taught by Ahmed et al. (col. 2, lines 39-46), with a reasonable expectation of success absent evidence of criticality of the particular steps.
Regarding the limitation wherein the water-soluble polymer comprises hydrophilic cellulosic polymer in an amount of at least 10%, Ahmed et al. does not specifically teach the exact amounts claimed in instant claim 1. However, it would be within the skill of an ordinary artisan to be able to modify the concentration in order to obtain the desired bioavailability of the agent. It is noted that "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Regarding the limitations “wherein less than 77% of apixaban dissolves within 30 minutes in a pH 6.8 phosphate buffer containing 0.05% sodium lauryl sulfate” and “the disintegration time of the film is less than 5 minutes”, when the composition recitations are met, the desired properties are met, as any component that materially affects the composition and its properties would have to be present in the claim to be commensurate in scope (i.e. claim 1). Additionally, when the composition is delivered in the same manner as claimed, the effects of the composition would be the same such as the dissolution profile, as they are a direct result of the components of the composition and the mode of administration which are met by the art, whereby the resulting properties and effects would intrinsically be met. A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). See MPEP 2112.01.
With regards to the limitation claimed in instant claim 11, which claims “the film comprises less than 10% of water content”, Ahmed et al. does not specifically teach the exact amounts claimed in instant claim 1. However, it would be within the skill of an ordinary artisan to be able to modify the concentration in order to obtain the desired dissolution of the active agent. It is noted that "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Even though the range for the amount of apixaban as taught by Lorbek et al. is not the same as the claimed amounts, Lorbek et al. does teach an overlapping range of amounts, and it has been held that in the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). See MPEP § 2144.05(I). Furthermore, the determination of the amount of an active agent is well within the purview of those skilled in the art through routine experimentation, and it has been held that “it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP § 2144.05(II). It would have been obvious to one of ordinary skill in the art to optimize the amount of apixaban in order to increase the efficacy of the composition.
The amounts of active agents to be used, the pharmaceutical forms, e.g., tablets, etc; mode of administration, flavors, surfactant are all deemed obvious since they are all within the knowledge of the skilled pharmacologist and represent conventional formulations and modes of administration.
Furthermore, no unobviousness is seen in the ratio claimed because once the usefulness of a compound is known to treat a condition, it is within the skill of the artisan to determine the optimum ratio.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Lorbek et al. (WO 2020/127819, as disclosed in IDS) and Ahmed et al. (US 10,709,662, as disclosed in IDS) as applied to claims 1-6, 8, and 10-12 above, and further in view of Mackman et al. (Therapeutic strategies for thrombosis: new targets and approaches, Nature Reviews Drug Discovery, 2020, 19, pp. 333-352).
The teachings of Lorbek et al. and Ahmed et al. are presented above.
Lorbek et al. and Ahmed et al. do not teach the film further comprising an additional active agent.
Mackman et al. is drawn towards therapeutic strategies for thrombosis (see abstract). Mackman et al. teaches “Antithrombotic agents fall into three classes — antiplatelet agents, anticoagulants and fibrinolytic agents. Because of the preponderance of platelets in arterial thrombi, antiplatelet agents are the mainstay for the prevention and treatment of AT. There are four main types of FDA- approved antiplatelet agents — a cyclooxygenase inhibitor (aspirin), P2Y12 antagonists (for example, clopidogrel, prasugrel and ticagrelor), αIIbβ3 antagonists (for example, abciximab) and a protease- activated receptor 1 (PAR1) antagonist (vorapaxar) (Box 1, Fig. 2).” (pg. 333, right column, 2nd paragraph).
It would have been obvious to one of ordinary skill in the art to formulate a film further comprising an additional active agent, as suggested by Mackman et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to do so since it is prima facie obvious to combine components known for the same purpose for their combined additive effects, with a reasonable expectation of success absent evidence of criticality of the particular formulation. Additionally, “[T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Therefore, it would have been prima facie obvious to combine apixaban and aspirin in a composition cojointly to treat thrombosis.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Lorbek et al. (WO 2020/127819, as disclosed in IDS) and Ahmed et al. (US 10,709,662, as disclosed in IDS) as applied to claims 1-6, 8, and 10-12 above, and further in view of Nause (CA 2,765,413, as disclosed in IDS).
The teachings of Lorbek et al. and Ahmed et al. are presented above.
Lorbek et al. and Ahmed et al. do not teach the film further comprising a flavorant.
Nause is drawn towards a solubility-improved form of apixaban for preventing or treating venous thromboembolisms, deep vein thrombosis and acute coronary syndrome (see abstract). Nause teaches apixaban compositions comprising flavorants (pg. 15, lines 3-6).
It would have been obvious to one of ordinary skill in the art to formulate a film further comprising a flavorant, as suggested by Nause, and produce the instant invention.
One of ordinary skill in the art would have been motivated to do so since flavorants have been conventionally formulated with apixaban as taught by Nause, with a reasonable expectation of success absent evidence of criticality of the particular formulation.
Conclusion
Claims 1-12 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREW P LEE whose telephone number is (571)270-1016. The examiner can normally be reached Monday-Friday 9am-5pm.
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/ANDREW P LEE/Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691
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