DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Election/Restrictions
Applicant’s election without traverse of Claims 1-14 and 17-19 directed to lurasidone microparticle formulations in the reply filed on 18 June 2026 is acknowledged.
Status of the Claims
Claims 1-20 are pending.
Claims 15, 16, and 20 are withdrawn from consideration as directed to non-elected inventions.
Claims 1-14 and 17-19 are presented for examination and rejected as set forth below.
Priority
The instant application is a Continuation-in-part of earlier application 17/679,385 filed 1 February 2022, which claims the benefit of each of Provisional U.S. applications 63/267,403 filed 1 Feb 2022 and 63/152,943 filed 24 February 2021.
Claim Interpretation
Applicants claims are directed to formulations of microspheres having an average particle size of less than or equal to 25 microns combining a biodegradable acid-terminated PLGA polymer having an inherent viscosity within a defined range and lurasidone, with lurasidone representing greater than 55% by weight of the microspheres. Dependent claims specify that the lurasidone is lurasidone HCl, or that the biodegradable polymer is an acid-capped PLGA, more specifically an acid-terminated PLGA polymer having a 85:15 ratio of lactide to glycolide or PLGA polymers having defined molecular weight ranges, specify a particular range of lurasidone drug loading, or narrow the dimensions the particles are to possess or the inherent viscosity the polymers are to possess. Additional dependent Claims specifying the composition is a “pharmaceutical”; art describing the use of such compositions to treat disease will be considered, in the absence of a particular specification that the composition is to be used as a pharmaceutical, sufficient to address this claim. Additional dependent claims recite certain lurasidone release parameters the composition is to possess.
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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 1, 3-7, and 10-14 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Vanover (U.S. PGPub. 2016/0310502) in view of Karavas (WO2014/202214)(of record in parent).
Vanover describes long-acting injectable microsphere compositions containing antipsychotic agents including lurasidone. [0084; 0086; 0092-93]. Vanover indicates these compositions can be obtained by dispersing the agents to be delivered in a polymeric matrix, which may be a PLGA polymer matrix of 85:15 lactide to glycolide, or alternatively an acid-terminated 75:25 PLA/PGA polymer. [0099; 0109]. Vanover indicates that these PLGA polymers may have molecular weights falling within the range of 20-200kD, such as 24kD, addressing limitations of Claims 13 and 14. [0116]. These polymer matrices are described by Vanover as particularly suited for providing injectable delayed or sustained release formulations that can deliver the load of agent completely over a period of 60 days. [0100; 0178]. While Vanover does not specify the degree to which the release of agent may be delayed, Vanover describes advantages in terms of pharmacokinetics and side effects achieved by providing delayed and sustained release dosage forms. [0102]. Armed with this information, a person of ordinary skill in the art would reasonably have expected that the rate of release is a result-effective variables that achieve the beneficial changes to pharmacokinetics and side-effect profiles Vanover ascribes to modifying the delay and release of agents from the PLGA microspheres. As such, it would have been routine to optimize the rate of agent release from within the total composition suggested by Vanover. See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (indicating that where 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.). Vanover indicates that the microspheres may possess a D50 of, for example, 10, 20, or 25 microns, addressing limitations of Claims 1, 3, 7, and 17. [0118-19]. See In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003) (“A prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art.”). Vanover likewise advocates using PLGA polymers having an inherent viscosity of between about 0.1-1dL/g, overlapping and therefore rendering obvious the limitations of Claims 1, 10 and 17. [0121].
While Vanover describes acid-terminated 85:15 PLA/PGA polymers as well as acid-end capped PLGA polymers having molecular weights of 20 or 24kD as polymer matrices for formulating microspheres of 10 or 20 microns loaded with antipsychotics such as lurasidone to provide for a variety of sustained and delayed release profiles, Vanover does not specify that the drug load of antipsychotics such as lurasidone should be in excess of 55% of the microsphere composition.
Karavas also describes injectable PLGA microparticles for releasing active pharmaceutical agents. (Abs.). Karavas indicates that some challenges are understood to be overcome when formulating basic/nucleophilic drug substances (drug agents possessing tertiary nitrogen atoms). (Pg.6, L. 11-26). A particular agent requiring such formulation is the atypical antipsychotic risperidone, which can possess a delayed and sustained release profile when formulated in PLGA microspheres. (Pg.7, L.1-21). Karavas indicates that these problems may be overcome with particular PLGA compositions having a high loading of agent (>20%) which initially release a small amount of agent, defining a range of concentrations which overlap and therefore render obvious the limitations of the instant claims. (Pg.8, L.9-20), see Peterson, supra. PLGA polymers having lactic acid: glycolic acid ratios of Vanover as well as the instantly claimed 85:15 as well as average particle sizes and molecular weight ranges overlapping both Vanover and the instant claims are described. (Pg.11, L.25 – Pg.12, L.8).
Because Karavas also describes loading 85:15 PLGA microparticles with basic antipsychotic drugs such as risperidone to levels in excess of 20%, and the lurasidone of both the instant claims and the Vanover reference possesses not only gross structural similarities to risperidone, but also includes multiple tertiary amines which Karavas indicates qualifies an agent as basic/nucleophilic within the understanding of their teachings, it would have been prima facie obvious to have included the antipsychotic lurasidone at concentrations over 55%, a range overlapping and therefore rendering obvious that of the instant claims, in the 85:15 PLA:PGA ratio PLGA matrices taught by Vanover to provide pharmaceutical dosage forms having improved delayed and sustained release properties.
Claims 1-7 and 10-14 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Vanover and Karavas as applied to claims 1, 3-7, and 10-14 above, and further in view of Kulkarni (WO2018/015915)(of record in parent).
Vanover and Karavas, discussed in greater detail above, suggest forming injectable pharmaceutical compositions employing acid-terminated 85:15 PLA/PGA polymers or acid-capped PLGA polymers having defined molecular weight ranges as polymer matrices for formulating microspheres of less than 25 microns loaded with concentrations in excess of 55% of antipsychotics such as lurasidone.
Neither Vanover nor Karavas specify that the lurasidone to be employed is the lurasidone HCl of the instant Claims.
This is cured by the teachings of Kulkarni, which indicates that the commercially available form of lurasidone is in fact the hydrochloride salt. (Pg.2, L.3-6).
It would have been prima facie obvious to have used lurasidone hydrochloride as the lurasidone in the injectable delayed-sustained release PLGA microparticles suggested by the teachings of Vanover and Karavas because it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945) (indicating that "Reading a list and selecting a known component to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle. It is not invention.”).
Claims 1-14 and 17-19 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Vanover, Karavas, and Kulkarni as applied to claims 1-7 and 10-14 above, and further in view of Martins (Claudia Martins, et al, Functionalizing PLGA and PLGA Derivatives for Drug Delivery and Tissue Regeneration Applications, 7 Adv. Healthcare Mater. 1701035 (2018)).
Vanover, Karavas, and Kulkarni discussed in greater detail above, suggest forming injectable pharmaceutical compositions employing acid-terminated 85:15 PLA/PGA polymers as polymer matrices for formulating microspheres of less than 25 microns loaded with concentrations in excess of 55% of antipsychotics such as lurasidone.
Neither Vanover nor Karavas specify that the 85:15 PLGA is to be acid-capped.
This is cured by the teachings of Martins, which establishes that each of molecular weight of the polymer, the ratio of lactic to glycolic acid units present in the polymer, as well as the presence of either the natural carboxylic acid end-group or an alternative cap influences the rate at which PLGA polymers degrade to release active agents incorporated within implanted matrices. (Pg.4-5). Increasing molecular weight as well as relative amount of lactic acid present in the polymer contribute to longer time to complete degradation, and therefore release, times, while retention of the naturally occurring carboxylic acid end groups demonstrates more rapid degradation than end-capped versions of the polymer. (Id.)
It would have been prima facie obvious for a skilled artisan to have utilized an carboxylic acid end-capped PLGA as the PLGA in the dosage forms suggested by each of Vanover, Kauravas, and Kulkarni, as set forth above. This is not only because Martins establishes that carboxylic acid end groups are the ordinary form of PLGA used as drug delivery matrices, but also because the retention of the terminal acid groups provides for predictable adjustment of PLGA degradation times, and therefore the release of drugs contained therein. Utilizing the unmodified PLGA copolymers which retain their acidic end groups as the PLGA polymer in drug release compositions simply represents the use of a compound known in the art to be suitable for such a purpose, and obvious thereby.
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 1-7 and 10-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 11,992,559. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘559 patent fall within and therefore render obvious the scope of the invention set forth by the present claims.
Conclusion
No Claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN M BASQUILL whose telephone number is (571)270-5862. The examiner can normally be reached Monday through Thursday, 5:30 AM to 4 PM.
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/SEAN M BASQUILL/Primary Examiner, Art Unit 1614
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