DETAILED ACTION
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 .
Applicant’s arguments, filed 11/09/2025, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Status
Claims 1-3, 5, 6, 8, and 9, are pending and under examination.
Claim Interpretation
The examiner best understands non-porous as having the same meaning as a smooth surface, which is defined as having an intact and smooth shape without flaws, depressions, protrusions, defects, or gaps, as recited in paragraph 52 of the instant specification (see ¶ 52).
Claim Rejections - 35 USC § 112(a) - New Matter
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-3, 5, 6, 8, and 9, are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1, as newly amended, recites the limitation “without solvent evaporation.” This limitation does not appear to be supported by the instant specification where the disclosed formulation method involves the step of solvent evaporation (see step 6 on ¶ 89). Likewise, the comparative examples are also prepared with a solvent evaporation step. Therefore the limitation appears to be new matter.
Claim 1 also recites “without… porogen.” This limitation does not appear to be supported by the instant specification where there is no mention of porogens. Any negative limitation or exclusionary proviso must have basis in the original disclosure. The mere absence of a positive recitation is not basis for an exclusion. See MPEP 2173.05(i). Here, a smooth surface does not inherently require the absence of porogens, where there are many factors that can influence surface texture, and porogens could act on the internal structure of the microparticles, while still having a smooth surface. Therefore, the limitation appears to be new matter.
Claims 2, 3, 5, 6, 8, and 9, are also rejected for the same reasons for depending upon rejected claim 1.
Claim Rejections - 35 USC § 112(b) or pre-AIA 2nd ¶
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.
Claims 1-3, 5, 6, 8, and 9, are 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 1 recites a “particle size distribution width (D90-D10),” and it is unclear if the “(D90-D10)” limitation is intended to define how the particle size distribution width is measured, an example of how it could be measured, etc. Further, adding to the lack of clarity, it does not appear that the particle size distribution widths of the working embodiments of the instant specification were measured as D90-D10, which suggests there are other ways in which the particle size distribution width can be measured. For example, table 1, preparation example 1A has a D90 of 41.26 microns and a D10 of 32.12 microns, and lists the particle size distribution width to be 7.24 microns, which is not calculated as D90-D10 (41.26 - 32.12 = 9.24). For purposes of examination, the examiner is interpreting particle size distribution width to be measured as the D90-D10.
Claims 2, 3, 5, 6, 8, and 9, are also rejected for the same reasons for depending upon rejected claim 1.
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
Claims 1-3, 5, 6, 8 and 9, stand rejected under 35 U.S.C. 103 as being unpatentable over Kim et al (WO 2019078583 A1, hereinafter “Kim ‘583”), in view Kim et al (US 20180133677 A1, hereinafter “Kim ‘677”).
Kim ‘583 teaches sustained release microparticles comprising a biodegradable polymer and a drug, wherein the biodegradable polymer and the drug are evenly distributed in the microparticles, and wherein the microparticles are composed of uniform-sized particles (constant average diameter), with an average particle diameter of 20 to 70 microns (¶¶ 1, 18, 19, 80). The fixed micro-size diameters can reduce foreign body sensation and pain during application as an injectable drug (abs). The drug release rates are shown in figures 7-10 (fig 7-10). The microparticles are spherical (¶ 19) with a smooth surface (¶ 76). A SEM image of the particles is disclosed by figures 4 and 5 (fig 4, 5). Embodiments comprising PLGA (includes poly-L-lactic acid, polyglycolic acid, poly-D-lactic acid-co-glycolic acid, poly-L-lactic acid-co-glycolic acid, poly-D,L-lactic acid-co-glycolic acid (¶ 5) with donepezil (IVL D1-4), naltrexone (IVL N1-N4), exenatide (IVL E1-4), aripiprazole (IVL A1-4), olanzapine (IVL Z1-4), minocycline (IVL C1-4), planosetron (IVL P1-4), octreotide (IVL O1-4), lanreotide (IVL L1-4), and liranglutide (IVL G1-4) are disclosed. Other suitable biodegradable polymers include poly-caprolactone, poly-valerolacton, poly-hydroxybutyrate, and poly-hydroxyvalerate (¶ 20). The microparticles provide sustained-release for 1 week to 3 months (¶ 17). The uniform particle sizes maintains a long-term administration with maintaining the drug concentration at a constant level (¶ 18). The microparticles have a biodegradable polymer to drug weight ratio ranging from 2:1 to 9:1 (¶ 23). The sustained release microparticles are prepared by dissolving a biodegradable polymer and a drug in organic solvent to produce a first mixture, dissolving a surfactant and water to produce a second mixture, injecting the first and mixture into microchannels, collecting the microparticles produced at the intersection, stirring the microparticles and evaporating and removing organic solvent, and washing and drying the microparticles (¶ 33). By slowly evaporating the organic solvent present on the surface of the microparticles, microparticles with a smooth surface can be manufactured (¶ 76).
Kim ‘583 does not specifically teach the particle size distribution as instantly claimed, nor the specific surface area per unit mass of the microparticles, nor the blood concentration ratio of claim 7.
Kim ‘677 teaches a polymer based drug delivery system comprising sustained release microspheres (microparticles) comprising a biodegradable polymer and a drug (title, ¶ 7), wherein the microparticles are monodisperse (i.e., having a narrow size distribution), with can have an overall particle size distribution of less than 1% (title, ¶¶ 1, 5, 522, fig 9). Particle size was measured using a particle size analyzer (¶ 457). A wide particle size distribution results in smaller particles have a short degradation time, and the larger particles being difficult to inject (¶ 147). Microspheres with a narrow particle size distribution have a tightly controlled duration and drug release (¶ 502). Kim ‘677 further discloses embodiments where particle size distributions of 16.65 and 19.95 microns were known (¶¶ 414, 415)
Regarding the drug release properties of claim 1, the release rates shown by Kim ‘583 are sustained-release, and appear to not have an excessive initial (burst) release, as instantly claimed.
Regarding the particle size distribution width of claim 1, where Kim ‘583 teaches an average particle diameter of 20-70 microns with a uniform particle size, which is important for maintaining drug release at a constant level and reducing foreign body sensation, it would have been obvious to formulate the microparticles with known particle size distributions suitable for sustained release microparticles comprising a biodegradable polymer and a drug, such as 16.65 microns from the working examples, down to less than 1%, as taught by Kim ‘677, overlapping the claimed range. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Further, it would have been well within the relative skills of the skilled artisan to routinely optimize the particle size distribution of the microparticles, in order to achieve desired controlled drug release properties, etc.
Regarding wherein the particles are configured to exhibit a sustained release with a release profile as claimed in claim 1, Examiner notes that the limitation is directed to the intended use of the microparticles, and the Cint and Cmax values would require administering the microparticles and subsequently measuring blood concentration. Even so, where the microparticles made obvious above appear to have the same structure, for the reasons discussed above, the functional properties are inherent to the microparticles, and therefore, the limitation is met. See MPEP 2112(II) and (III).
Regarding the specific surface area per unit mass of claim 1, where the microparticles comprise a biodegradable polymer, a drug, are spherical, have a smooth surface, and an average diameter of 20-70 microns with a narrow size distribution width, and appear to be formulated via substantially the same process to the process recited in the instant specification, it appears the structure of the microparticles are the same, and therefore, it appears the specific surface area per unit mass is inherent to the structure of the microparticles. See MPEP 2112(II) and (III). This is further supported by the instant specification, which evidences the sustained-release microparticles of the present invention are monodisperse, have a smooth surface, a spherical shape (see pg 14 of the instant specification), and claim 6 shows that an average diameter from 20-100 microns is suitable (see instant claim 6). Additional support is provided by table 1 of the instant specification which shows that solid round particles having the above mentioned properties have specific surface areas that fall within the claimed values (see table 1 of the instant specification).
Regarding wherein the microparticles are formulated without solvent evaporation or porogen of claim 1, while these limitations appear to be new matter for the reasons discussed above, the examiner notes that the limitations are product by process limitations, and where the microparticles made obvious above appear to comprise the specific surface area as instantly claimed, the limitations are met. Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process. See MPEP 2113(I).
Regarding claim 2, where the only components of the microparticles are the biodegradable polymer and drug, and where the biodegradable polymer to drug weight ratio ranges from 2:1 to 9:1, the weight ratio of biodegradable polymer to drug is equal to the weight percent based on the weight of the microparticles. Therefore, the weight percent of biodegradable polymer ranges from 66-90 wt% of the microparticle, overlapping the claimed range. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Regarding claim 3, it would have been obvious to formulate the microparticles with a biodegradable polymer to drug weight ratio ranges from 2:1 to 9:1, as taught by Kim ‘583, overlapping the claimed range. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Regarding claim 5, it would have been obvious to select from poly-L-lactic acid, polyglycolic acid, poly-D-lactic acid-co-glycolic acid, poly-L-lactic acid-co-glycolic acid, poly-D,L-lactic acid-co-glycolic acid, poly-caprolactone, poly-valerolacton, poly-hydroxybutyrate, and poly-hydroxyvalerate, as the biodegradable polymer, as motivated by Kim ‘583.
Regarding claim 6, it would have been obvious to formulate the microparticles with an average diameter between 20-70 microns, as taught by Kim ‘583, falling within the claimed range. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Regarding claim 8, it would have been obvious to formulate the microparticles for a release period from 1 week to 3 months, depending on the desired drug, as taught by Kim ‘583, overlapping the claimed range. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Regarding claim 9, it would have been obvious to select from donepezil, naltrexone, and exenatide, as the drug, as taught by Kim ‘583.
Response to Arguments
First, Applicants assert that specific surface area (SSA), surface morphology, and drug release behavior (Cint/Cmax) is not taught or suggested by the prior art. Applicants assert the particle size distribution width of Kim '677 of <1% is much narrower than the claimed 7-16 microns. Applicants assert the cited art does not provide any motivation to select the claimed absolute width, which was optimized for reproducible injectability and controlled release.
Second, Applicants assert specific surface area (SSA) is not inherent to particle size and shape, and that the declaration clearly shows that SSA is influenced not only by size and shape, but by surface roughness, porosity, and internal morphology. Applicants assert comparative ex. 3 in table 2 has a D50 size comparable to example 1 but differs in SSA due to its porous surface, and that these differences are confirmed visually by SEM images (fig. 15A, 15B) and numerically by SSA values.
Third, Applicants assert the claimed microparticles are formed without solvent evaporation or porogen, resulting in non-porous surface - in contrast to the porous structures in Kim '583 (see fig. 15A). Argue this is a result of the manufacturing method, which is structurally and functionally distinct from the prior art.
Fourth, Applicants assert the in vivo drug release profile is not an intended result but a direct outcome of the particle's structural properties, including: narrow and controlled particle size width, non-porous, smooth surface, SSA within a narrow defined range. Applicants assert table 4, example 1 shows a Cint/Cmax of 1:4.0 vs 1:1.2 for Vivitrol®, and comparative ex. 3 does not satisfy the Cint/Cmax requirement despite similar particle size, underscoring the structural-functional relationship.
Fifth, Applicants assert the declaration affirms that this unique combination produces a synergistic effect that enhances pharmacokinetic control and reproducibility - features that are not predictable form the individual teachings of Kim '583 or Kim '677.
First, respectfully, this argument is not persuasive. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). As discussed above, where Kim ‘677 teaches a particle size distribution of less than 1%, the reference also teaches particle size distributions in working embodiments of 16.65 microns, it would have been obvious for the skilled artisan to start with 16.65 microns and adjust down to less than 1%, overlapping the instantly claimed range, for the same reasons discussed above and of record.
Second, respectfully, this argument is not persuasive. The examiner agrees that the specific surface area is a product of the particle size, shape, surface roughness, and structure of the microparticles, as previously discussed. Applicants point to ex. 3 in table 2 and compares the data to "Example 1," however, it is not clear to the examiner what "Example 1" is, as there are no embodiments disclosed in the instant specification as "Example 1." Table 1 of the instant specification recites a preparation example 1A and 1B, however, the D50 values of 35.70 and 36.32 microns, respectively, do not appear to be close to those of comparative example 3, which recites a D50 of 77.05 microns (over double the size). Preparation examples 5 and 6 recite D50 values of 72.69 and 73.05 microns, respectively, which is closer to comparative example 3, but also have specific surface areas within 0.005 m^2/g of each other. The examiner notes that preparation examples 5 and 6 also comprise different drugs, drug content, and polymer content than those of comparative example 3. The closest direct comparison to comparative example 3 appears to be preparation example 3, however, the D50 of the comparative example 3 is nearly double the size of those of preparation example 3 (77.05 vs 40.01 microns). Accordingly, contrary to applicant's assertion, it is respectfully not seen where the instant specification or the declaration clearly shows that the SSA differs with comparable D50 sizes in directly comparable compositions, let alone that this difference is due to variations in porosity.
Third, respectfully, this argument is not persuasive. Applicants have amended claim 1 to recite that the microparticles are formed without solvent evaporation or porogen, which appears to be new matter as discussed above, however, this limitation is simply a product by process limitation. Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process. See MPEP 2113(I). Applicants assert that the structures in Kim '583 are porous and points to fig. 15A for support, however fig. 15A is not disclosed by Kim '583, but is instead a SEM image of comparative ex. 3 of the instant disclosure. Kim '583 explicitly teaches the surface of the microparticles are smooth, suggesting the surface lacks porosity, and the particles appear to be formulated by substantially the same process as those instantly claimed, as discussed above. There appears to be no teachings in Kim '583 of the microparticles being porous or comprising porogens. While the microparticles of Kim '583 recite embodiments prepared with a solvent evaporation step, the instant specification also recites that the nanoparticles are formulated with a solvent evaporation step, both appearing to have substantially the same method of production. Accordingly, where the microparticles made obvious above comprise the same polymers, drugs, particle size distribution, a smooth surface, and appear to be formulated by substantially the same process, the structure of the microparticles made obvious above appear to be the same as those instantly claimed.
Fourth, respectfully, this argument is not persuasive. As previously discussed, the limitation of the Cint/Cmax is tied to the intended use of the microparticles, where the Cint/Cmax values would require administering the microparticles and subsequently measuring blood concentration. The examiner agrees with Applicants that the microparticle structure plays a role in the drug release profile, and where the microparticles made obvious above appear to have the same structural properties as those instantly claimed, the functional properties of the Cmax/Cint limitation appear to be inherent to the microparticles themselves. See MPEP 2112(II) and (III). Applicants assert example 1 in table 4 shows a Cint/Cmax of 1:4.0 vs 1:1.2 for Vivitrol®, however, there are no testing groups in instant table 4 that refer an “example 1,” and the examiner is not sure what results Applicants are referring to. Additionally, it does not appear that any of the embodiments shown in table 4 have a 1:4.0 or a 1:1.2 Cint/Cmax ratio, as asserted by Applicants.
Fifth, respectfully, this argument is not persuasive. Applicants assert that the claimed combination yields unexpected and beneficial pharmacokinetic properties, but again, it is not clear what properties Applicants are asserting are unexpected. If Applicants are asserting no initial excessive release of the drug with the claimed combination is unexpected, Kim ‘583 already appears to teach no initial excessive release with a uniform-particle sizes. If Applicants are asserting the limitation of wherein the microparticles are configured to exhibit a specific release profile in vivo is unexpected, this limitation is tied to an intended use limitation, and where the microparticles made obvious above appear to have the same structure, the functional properties are inherent to the microparticles for the same reasons discussed above.
Claims 1-3, 5, 6, 8 and 9, stand rejected under 35 U.S.C. 103 as being unpatentable over Kim et al (WO 2019078583 A1, hereinafter “Kim ‘583”), in view of Kim et al (US 20180133677 A1, hereinafter “Kim ‘677”), and Srinivas et al (US 20080226742 A1, hereinafter “Srinivas”).
Kim ‘583 and Kim ‘677 are discussed above, and purely arguendo, if somehow the specific surface area of the microparticles made obvious above are not inherent, the following applies.
Srinivas teaches non-porous polymeric microparticles for controlled release of bioactive agents (abs, ¶ 12). Substantially non-porous microparticles were known to allow for better control over drug release (¶ 44). Porosity can be altered by controlling the processing parameters during the manufacture of the microparticle, etc., such as by slowing the solvent evaporation (¶ 44). The microparticles can have surface areas ranging from about 0.01 to about 500 m2/g, with embodiments comprising 0.1696 m2/g, 0.1865 m2/g, 0.2054 m2/g, etc. (¶¶ 46, 97, 102, 106, claim 1).
It would have been obvious to formulate the microparticles made obvious above in view of Kim ‘583 and Kim ‘677 for the same reasons discussed above, as applied to each and every claimed limitation.
It would have been obvious to modify the microparticles made obvious above by formulating the microparticles with known surface areas suitable for sustained release polymeric microparticles, such as from about 0.01 to about 500 m2/g, including 0.1696 m2/g, 0.1865 m2/g, 0.2054 m2/g, etc., as taught by Srinivas, where these surface areas are suitable for non-porous microparticles that allow for better control over drug release. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Further, it would have been well within the relative skills of the skilled artisan to routinely adjust the surface area of the microparticles, in order to achieve desired consisted release profiles, etc. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[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. See MPEP 2144.05(II)(A).
Nonstatutory Double Patenting
Claims 1-3, 5, 6, 8, and 9, stand provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending Application No. 18/434,686 (reference application), hereinafter referred to as ‘686, in view of Kim et al (WO 2019078583 A1, hereinafter “Kim ‘583”), Kim et al (US 20180133677 A1, hereinafter referred “Kim ‘677”), and Srinivas et al (US 20080226742 A1, hereinafter “Srinivas”). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘686 disclose microparticles comprising moxidectin (drug) and a biodegradable polymer, wherein the drug is uniformly distributed in the spherical biodegradable polymer (claim 1). The microparticles have an average diameter of 45-120 microns, and has a polymer to drug weight ratio of 9:1 (claim 1). The microparticles are spherical (claims 1 and 4). The drug is released from 3 to 6 months, and the biodegradable polymer is polylactide (PLA).
‘686 does not disclose the particle size distribution of claim 1, specifically disclosing the surface area per unit mass of claim 1, the drugs of claims 1 and 9, nor specifically disclose the functional limitations of claim 7.
Kim ‘583 and Kim ‘677, are discussed above.
It would have been obvious to modify ‘686 based on the teachings above.
Regarding the particle size distribution of claim 1, it would have been obvious to formulate the microparticles with known particle size distributions suitable for sustained release microparticles comprising a biodegradable polymer and a drug, such as 16.65 microns from the working examples, down to less than 1%, as taught by Kim ‘677, for the same reasons discussed above. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Where the microparticles are structurally identical and have the same particle size as those instantly claimed, it follows that the PLA microparticles must inherently exhibit the same specific surface area per unit as instantly claimed. See MPEP 2112(I) and (II).
If a smooth surface on the microparticles is required for the specific surface area per unit as instantly claimed, it would have been obvious to formulate smooth particles, as taught by Kim ‘583, where smooth particles were known to be suitable for sustained release microparticles.
Purely arguendo, if the specific surface area is not inherent, it would have been obvious to formulate non-porous (i.e., smooth) microparticles with known specific surface areas suitable for sustained release microparticles comprising a polymer and a drug, such as those taught by Srinivas above, for the same reasons discussed above and of record.
It would have been obvious to select from drugs that are taught to be suitable for sustained release microparticles, such as those taught by Kim ‘583 above.
Regarding the release profile of claim 1, Examiner notes that the limitation is directed to the intended use of the microparticles, and the Cint and Cmax values would require administering the microparticles and subsequently measuring blood concentration. Where the microparticles made obvious above appear to have the same structure, for the reasons discussed above, the limitation is met. See MPEP 2112(II) and (III).
Where the microparticles made obvious above are structurally identical and have the same particle size distribution width as those instantly claimed, and comprises the claimed drugs, the functional limitation of the ratio of initial blood concentration and maximum blood concentration of 1:2 to 1:30 would inherently flow from the microparticle composition. See MPEP 2112(II) and (III).
With regards to claim 6, it would have been obvious to formulate the microparticles with a diameter of 45-120 microns, as disclosed by ‘686. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The following also stand rejected for comprising microparticles comprising a biodegradable polymer and a drug for sustained release, based on the modifications discussed above in view of Kim et al (WO 2019078583 A1, hereinafter “Kim ‘583”), Kim et al (US 20180133677 A1, hereinafter referred “Kim ‘677”), and Srinivas et al (US 20080226742 A1, hereinafter “Srinivas”):
Copending Application No. 18/285,002
Copending Application No. 18/284,981
Response to Arguments
Applicants assert that the references do not disclose or teach all of the features as recited in the amended claims.
Examiner disagrees. The claims stand rejected for the same reasons above and of record.
Claims 1-3, 5, 6, 8, and 9, stand rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent No. 11911508 B2, hereinafter referred to as ‘508, in view of Kim et al (WO 2019078583 A1, hereinafter “Kim ‘583”), Kim et al (US 20180133677 A1, hereinafter referred “Kim ‘677”), and Srinivas et al (US 20080226742 A1, hereinafter “Srinivas”). Although the claims at issue are not identical, they are not patentably distinct from each other because ‘508 discloses sustained release microparticles comprising a biodegradable polymer and dutasteride (drug), wherein the microparticles have a dutasteride drug evenly distributed in a spherical biodegradable polymer, have an average particle diameter of 20 to 70 μm, contain the biodegradable polymer and drug at a weight ratio of 3:1 to 9:1, and are capable of continuous drug release for 1-3 months without initial excess release (claim 1). The biodegradable polymer is selected from polylactide-co-glycolide (PLGA), etc.
‘508 does not disclose the particle size distribution of claim 1, specifically disclosing the surface area per unit mass of claim 1, the release properties of claim 1, nor the drugs of claims 1 and 9.
Regarding the particle size distribution of claim 1, it would have been obvious to formulate the microparticles with known particle size distributions suitable for sustained release microparticles comprising a biodegradable polymer and a drug, such as 16.65 microns from the working examples, down to less than 1%, as taught by Kim ‘677, for the same reasons discussed above. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Where the microparticles are structurally identical and have the same particle size as those instantly claimed, it follows that the PLA microparticles must inherently exhibit the same specific surface area per unit as instantly claimed. See MPEP 2112(I) and (II).
If a smooth surface on the microparticles is required for the specific surface area per unit as instantly claimed, it would have been obvious to formulate smooth particles, as taught by Kim ‘583, where smooth particles were known to be suitable for sustained release microparticles.
Purely arguendo, if the specific surface area is not inherent, it would have been obvious to formulate non-porous (i.e., smooth) microparticles with known specific surface areas suitable for sustained release microparticles comprising a polymer and a drug, such as those taught by Srinivas above, for the same reasons discussed above and of record.
It would have been obvious to select from drugs that are taught to be suitable for sustained release microparticles, such as those taught by Kim ‘583 above.
Regarding the release profile of claim 1, Examiner notes that the limitation is directed to the intended use of the microparticles, and the Cint and Cmax values would require administering the microparticles and subsequently measuring blood concentration. Where the microparticles made obvious above appear to have the same structure, for the reasons discussed above, the limitation is met. See MPEP 2112(II) and (III).
The following also stand rejected for comprising sustained release microparticles comprising a biodegradable polymer and a drug, based on the modifications discussed above in view of Kim et al (WO 2019078583 A1, hereinafter “Kim ‘583”), Kim et al (US 20180133677 A1, hereinafter referred “Kim ‘677”), and Srinivas et al (US 20080226742 A1, hereinafter “Srinivas”):
U.S. Patent No. 11931461 B2
U.S. Patent No. 11504688 B2
U.S. Patent No. 11344624 B2
Response to Arguments
Applicants did not provide arguments for the double patenting rejections over the U.S. Patents listed above. Accordingly, the claims stand rejected for the same reasons above and of record.
Claims 1-3, 5, 6, 8, and 9, stand provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending Application No. 17/723,155 (reference application), hereinafter ‘155. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘155 disclose sustained release microparticles comprising a biodegradable polymer and donepezil, wherein the biodegradable polymer and donepezil are evenly distributed, the microparticles are uniform-sized particles that do not show an initial excessive release of the donepezil and have a particle size distribution of 35 microns or less (claim 1). The particles have a specific surface area per unit mass as instantly claimed (claim 1). The particles exhibit sustained release from 1 week to 12 months (claim 1). The biodegradable polymer is 60-97 wt% of the microparticles (claim 2). Donepezil is contained in a weight ratio of 30:1 to 1.5:1 compared to the biodegradable polymer (claim 3). The biodegradable polymer are those of instant claim 5 (claim 4). The microparticles have an average diameter between 20 micron and 100 micron and have a smooth spherical surface (claim 5). The donepezil released from the microparticles have an initial blood concentration to the maximum blood concentration ratio of 1:2 to 1:30 (claim 6).
Regarding the newly amended particle size distribution, where the claims of ‘155 disclose a particle size distribution width of 35 microns or less, it would have been obvious to formulate the microparticles with a particle size distribution width within that range, such as those instantly claimed. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicants assert that claim 1 has been amended and requests withdrawal of the double patenting rejection.
The double patent rejection over the claims of ‘155 has been updated to reflect the newly amended claims, and is obvious for the reasons discussed above.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/JOSHUA A ATKINSON/Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612