DETAILED ACTION
Status of Application
The Examiner acknowledges receipt of the amendments filed on 9/4/2025 wherein claim 1 has been amended and claim 5 has been cancelled.
Claims 1-4 and 6 are presented for examination on the merits. The following rejections are made.
Response to Applicants’ Arguments
Applicant’s amendments/arguments filed 9/4/2025 overcome the rejection of claims 1-6 made by the Examiner under 35 USC 103 over Guo et al. (Asian J Pharm Sci, 2015, 405-414) in view of Berkland et al. (J Controlled Release, 73, 2001, 59-74). This rejection has been withdrawn.
Applicant’s arguments filed 9/4/2025 regarding the rejection of claims 1-4 and 6 made by the Examiner under nonstatutory double patenting over 17/762701 have been fully considered but they are not found persuasive and is MAINTAINED for the reasons of record in the office action mailed on 6/5/20255.
In regards to the double patenting rejection, Applicant asserts the following:
The present application has been amended and the rejection should be withdrawn.
In response to A, the claims of the reference application are directed to “sustained-release microparticles comprising a biodegradable polymer and a drug wherein the biodegradable polymer and the drug are evenly distributed in the microparticles the microparticles are composed of uniform-sized particles that do not show an initial excessive release of the drug and have a particle size distribution width analyzed by the particle size analyzer of 35 microns or less the microparticles are composed of uniform-sized particles that do not show an initial excessive release of the drug and have a particle size distribution width (D90-D10), as measured by a particle size analyzer, of 7 um to 16 um the microparticles have a specific surface area per unit mass of 0.75x104to 2.0x 10'm/g and exhibit a sustained release pattern of the drug for a desired period the drug contained in the microparticles is selected from the group consisting of donepezil, aripiprazole, olanzapine, palonosetron, minocycline, memantine, naltrexone, alendronate, deoxycholate, risedronate, ibandronate, zoledronate, liraglutide, exenatide, lanreotide, octreotide, deslorelin, leuprorelin, goserelin, and triptorelin, and the microparticles are configured to exhibit a sustained drug release profile without initial excessive release, such that the ratio of the initial blood concentration (Cmt) to the maximum blood concentration (Cmax) is from 1:2 to 1:30, and the microparticles are formed without solvent evaporation or porogen, and as a result, exhibit a non-porous surface morphologv and a specific surface area of 0.75 x 10-1 to 2.0 x 10-1 m2/g.
The instant claims are directed to “sustained-release microparticles comprising: a biodegradable polymer; and Donepezil, wherein the biodegradable polymer and the Donepezil are evenly distributed in the microparticles the microparticles are composed of uniform-sized particles that do not show an initial excessive release of the Donepezil and have a particle size distribution width analyzed by the particle size analyzer of 35 microns or less, the particles have a specific surface area per unit mass of 0.75x10-1 to 2.0x10-1 m2/g, such that the microparticles exhibit sustained release of Donepezil for a period of at least 1 month and up to 12 months and the microparticles have an average diameter (D50) between 35.70 um and 73.05 um and have a smooth spherical surface.”
The major difference between the reference claims and those pending appear to be the particle size distribution. Although the pending claims do not limit a particle size distribution of 7-16 um, Table 1 of the instant specification shows that particles according to the invention can have a particle size distribution width of 8.69 for donepezil microparticles (see preparation Example 2).
The reference application 17/762701 is still overlapping with that claimed despite being amended. This argument is not considered persuasive.
Rejections
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.
Claims 1-4 and 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al. (WO 2019/078583; of record; translation provided) in view of Berkland et al. (J Controlled Release, 73, 2001, 59-74; of record).
Kim describes a sustained release microparticle containing a polymer such as PLGA (see page 4) (see instant claims 1 and 4) and a drug such as donepezil (see page 4) (see instant claim 1) wherein the microparticles contains the polymer and drug in a weight ratio of 2:1 to 9:1 (see page 7) (see instant claim 3). 2:1 to 9:1 equates to 66% to 90% polymer (math not shown). This range overlaps with the claimed range of 60-97% by weight (see instant claim 2). See MPEP 2144.05(I) regarding obviousness of overlapping ranges.
The microparticle’s of Kim are capable of sustained release for a period of time of one week to three months (see page 2) (see instant claim 1). Kim teaches that the microparticles are to be smooth and have a spherical shape (see page 4) and that the drug is uniformly distributed within the microparticle (see page 4) (see instant claim 1). The microparticles are to have a diameter of between 20-70 microns (see page 4) (see instant claim 1), wherein the microparticles are prepared by using a microchannel having a cross section of 0.7-1.3 with respect to the diameter of the microparticles thereby ensuring a homogenous particle distribution (see page 4). Kim teaches that particles having a size below 20 microns results in predation by macrophages post injection, possibly affecting absorption whereas particles with a size above 70 microns increase foreign body sensation and pain when administered (see page 8).
Figure 7 demonstrate the release characteristics of drug from the microparticle where it is observed that no initial excessive release of drug is observed (see instant claim 1).
Regarding instant claim 6, this is an intended use limitation in that it defines an initial blood concentration to maximum blood concentration. A blood concentration, however, would require that the particles be administered and a blood concentration be subsequently measured. The blood concentration is related to the act of administering the composition rather than to any structural feature of the composition claimed. See 2112.02 regarding statements of intended use.
Kim fails to teach the particle size distribution width as being 35 microns or less
Berkland is directed to the microspheres having precisely controlled monodisperse size distributions. The use of monodisperse microparticles is desirable in therapeutic endeavors as there is typically an ideal sphere size that provides a desired rate of release and route of administration. Spheres that are too small may exhibit poor encapsulation efficiency, may migrate from site of injection, and may exhibit undesirable release of the payload agent whereas particles that are too large may not easily pass through a syringe needle (see page 60). So, just as desired by Kim, particle size control would be a desired property for microspheres intended to be administered for the delivery of a therapeutic agent. Berkland teaches their technique can produce microspheres of a 30 micron diameter in which more than 95% of the particles are within 1.0-1.5 microns of the average (i.e. have a particle size distribution with of 35 microns or less) (see abstract and page 69, Figure 9). Modifying Kim’s such that the resulting microparticles would exhibit a monodisperse population like that described by Berkland would have been obvious as the use of a known technique to improve similar products in the same way is indicia of obviousness. See MPEP 2143(I)(C).
Regarding the limitation that the particles have a specific surface area per mass unit of 0.75x10-1 to 2.0x10-1 m2/g, as recited by instant claim 1, this property would be expected to flow from the obvious PLGA donepezil particles resulting from Kim and Berkland because the resulting particles would be identical in composition and structure with that claimed and thus would reasonably be expected to possess such a physical property.
Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was filed, as evidenced by the references, especially in absence of evidence to the contrary.
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 1-4 and 6 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5, 6, 8 and 9 of copending Application No. 17/762701 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the reference application like the instant invention is directed to a sustained-release microparticles comprising a biodegradable polymer and a drug, wherein the biodegradable polymer and the drug are evenly distributed in the microparticles, the microparticles are composed of uniform-sized particles that do not show an initial excessive release of the drug and have a particle size distribution width analyzed by the particle size analyzer of 35 microns or less, and the particles have a specific surface area per unit mass of 0.75×10-1 to 2.0×10−1 m2/g and exhibit a sustained release pattern of the drug for a desired period wherein the drug can be that of donepezil. Thus, the reference claims are overlapping with that instantly claimed with minimal distinction.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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/KYLE A PURDY/Primary Examiner, Art Unit 1611