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 .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 06/01/2026 has been entered.
Applicants' arguments, filed 06/01/2026, 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 Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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, and 8-11, are pending and under examination.
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, 10, and 11, are 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 Lee et al (WO 2020130585 A1, hereinafter "Lee").
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). The biodegradable polymer is selected from polylactide, etc. (¶ 56). 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 leuprorelin or deslorelin, the particle size distribution as instantly claimed, the span value as instantly claimed, nor the specific surface area per unit mass of the microparticles.
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 as measured by a particle size analyzer were known (¶¶ 414, 415). The references discussed span values (¶ 380). The average diameter is between 10 and 200 microns (¶ 158).
Kim’ 677 does not specifically teach deslorelin, nor the span value as instantly claimed.
Lee teaches sustained release microspheres comprising a deslorelin and a polylactide polymer, (title, ¶¶ 3, 13). The microspheres have an average particle size of 10-100 microns (¶ 14). The particle size is uniform, having a span value of 1.2 or less, more preferably 1.0 or less, with specific examples having a span value of 0.62 (D(0.9)-D(0.1)/D(0.5)) (¶ 21, table 2). Particle sizes of 100 microns or less with Span values of 1.2 microns or less, showed a high recovery rate and superior injectability (¶ 148). A uniform particle size distribution or span value allows for smaller deviation during injection and more accurate dosage compared to non-uniform microspheres (¶ 21). The sustained release microspheres have sustained release over 6 months, 3 months, 1 month, etc. (¶¶ 22, 23, 52, 53).
Regarding the drug release properties of claim 1, the release rates shown by Kim ‘583 are sustained-release, as instantly claimed.
Regarding the polylactide, it would have been obvious to select from polylactide as the biodegradable polymer, as motivated by Kim ‘583.
Regarding the drug, it would have been obvious to modify the combination above by selecting from other known active agents that were known to be suitable for sustained release microparticles comprising polylactide for sustained delivery, including deslorelin, as taught by Lee, depending on desired therapeutic activity and treatments.
Regarding the average diameter, 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 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. 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. 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. See MPEP 2144.05(II)(A).
Regarding the span value, it would have been obvious to modify the microparticles made obvious above with a span value of 1.0 or less, where Kim ‘583 teaches uniform particle sizes are important for maintain drug release at a constant level and reducing foreign body sensation, and where Lee teaches span values of 1.0 or less were preferred for polylactide microspheres for sustained release of an active agent, as these values were known to have a higher recovery rate, superior injectability, smaller deviation during injection, and more accurate dosage compared to non-uniform microspheres. 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 have routinely optimized the span value in order to achieve desired and optimal drug release, foreign body sensation, more accurate dosage, superior injectability, etc., which were known results effective variables as taught by Kim ‘583 and Lee above.
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 claim 3, it would have been obvious to include deslorelin for the same reasons discussed above by Lee.
Regarding claim 5, the microparticles of Kim are taught to have a smooth spherical surface, thereby meeting the claimed limitation.
Regarding claims 6 and 11, the sustained release times appear to be intended use limitations of the microparticles made obvious above, and where the Kim ‘583 teaches the particles are capable of sustained release for a period from 1 week to 3 months, the limitations are met. Purely arguendo, it not intended use, 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).
Further, the limitation appears to be intended use for the reasons discussed above, and where Lee teaches microparticles comprising an active agent and a polylactide particle are capable of sustained release over 6 months, it appears the particles made obvious above would be capable of being formulated for sustained release for 6 months, depending on the desired intended use. Purely arguendo, if not intended use, it would have been obvious to formulate the microparticles for a sustained release for 6 months, 3 months, 1 month, etc., which are taught to be suitable for sustained release microspheres comprising an deslorelin and a polylactide polymer, as taught by Lee, depending on the desired treatment time, severity of condition to be treated, etc. 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 the average diameter of claim 10, it would have been obvious to modify the microparticles made obvious above by adjusting the average diameter to those known to be suitable for sustained release microspheres comprising an active and a polylactide polymer, such as from 10-100 microns, as taught by Lee.
Regarding the particle size distribution width, 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, appearing to overlap 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. 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. See MPEP 2144.05(II)(A).
Regarding the span value, it would have been obvious to formulate the microparticles with a span value of 1.0 or less, for the same reasons discussed above by Lee.
Regarding the specific surface area, where the microparticles made obvious above comprise a biodegradable polymer, a drug, are spherical, have a smooth surface, and an average diameter of 10-100 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 meeting the claimed ranges (see table 1 of the instant specification).
Response to Arguments
First, Applicants assert Kim ‘583 does not teach the amended drug limitation.
Second, Applicants assert Kim ‘583 does not teach the presently claimed uniformity requirements including the span value.
Third, Applicants assert Kim ‘677 does not cure the deficiencies of Kim ‘583. Specifically, Applicants assert Kim ‘677 does not teach or suggest the claimed combination of polylactide, leuprorelin or deslorelin, particle size distribution width of 25 microns or less, span value of 0.5 or less, and the specific surface area as claimed. Applicants assert nothing in Kim ‘677 teaches or suggests these specific combinations.
Fourth, Applicants assert the claims are directed a specific combination of drug, polymer, particle size, particle size distribution width, span value, specific surface area, and sustained-release behavior, and asserts that the specification shows that this combination is associated with uniformly sized particles and distinguished the prior art which has much larger size distribution widths and span values.
Fifth, Applicants assert the dependent claims provided additional limitations that are not taught or suggested by the applied references for the same reasons previously discussed.
First, respectfully, this argument is not persuasive. Jin and Lee are newly cited above and make obvious the claimed drugs for the same reasons discussed above.
Second, respectfully, this argument is not persuasive. In view of the newly amended limitation, Lee is newly cited above and makes obvious the span values for the same reasons discussed above.
Third, respectfully, this argument is not persuasive. As discussed above, Jin and Lee are newly cited to make obvious to the newly amended limitation of wherein the active agent is leuprorelin or deslorelin. Regarding the particle size distribution, Kim ‘677 teaches specific embodiments where particle size distribution is 16.65 microns from the working examples, down to less than 1%, which appears to overlap the claimed range. Further, it would have been well within the relative skills of the skilled artisan to have routinely optimized the particle size distribution width for the same reasons discussed above, and where the general conditions of the concentrations are taught by the prior art. Regarding the span value, span values overlapping the claimed amounts are made obvious by newly added Lee for the same reasons discussed above. Finally, regarding the specific surface area, the specific surface area appears to be inherent to the structure of the microparticles, for the same reasons discussed above.
Fourth, respectfully, this argument is not persuasive. Applicants assert when considered as a whole, the instantly claimed combination is distinguished from the prior art in that they have uniform particle sizes with narrower particle size distribution widths and span values, however, Kim ‘583 teaches the particles are uniform in size, suggesting narrow particle size distribution and span values, Kim ‘677 teaches particle size distributions widths falling within the claimed range were known for polymer microspheres for sustained release, Lee teaches span values overlapping the claimed ranges were known, and smaller span values were preferred for polylactide microspheres for sustained release of an active agent, as these values were known to have a higher recovery rate, superior injectability, smaller deviation during injection, and more accurate dosage compared to non-uniform microspheres. Contrary to Applicants assertion, when the prior art is view as a whole, the prior art appears to make obvious the instantly claimed combination.
Fifth, respectfully, this argument is not persuasive. The additional limitations of the dependent claims, as newly amended, appear to be met of the same reasons discussed above and of record.
Claims 1-3, 5, 6, and 8-11, are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al (WO 2019078583 A1, hereinafter “Kim ‘583”), in view of Jin et al (US 20140314853 A1, hereinafter "Jin"), Kim et al (US 20180133677 A1, hereinafter “Kim ‘677”), and Lee et al (WO 2020130585 A1, hereinafter "Lee").
The references are discussed above but do not appear to teach leuprorelin.
Jin teaches microspheres for sustained release of therapeutic agents, wherein the microspheres comprise a biodegradable polymer including polylactic-co-glycolic acid, polylactic acid, etc. (i.e., polylactides) (abs, ¶¶ 16, 25, claim 8). Suitable active agents include leuprorelin, octreotide, etc. (¶ 16). The microspheres exhibited a spherical shape, a smooth surface, a diameter of around 60 microns, a narrow size distribution, and (¶ 42).
It would have been obvious to modify the combination above by selecting from other known active agents that were known to be suitable for sustained release microparticles comprising polylactide, a smooth surface, and a narrow particle size distribution, including leuprorelin, as taught by Jin, depending on the desired therapeutic activity and treatments.
Regarding the average diameter of claim 8, it would have been obvious to modify the microparticles made obvious above by adjusting the average diameter to those known to be suitable for sustained release microspheres comprising an active and a polylactide polymer, such as from 10-100 microns, as taught by Lee.
Regarding the particle size distribution width, 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, appearing to overlap 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. 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. See MPEP 2144.05(II)(A).
Regarding the span value, it would have been obvious to formulate the microparticles with a span value of 1.0 or less, for the same reasons discussed above by Lee.
Regarding the specific surface area, where the microparticles made obvious above comprise a biodegradable polymer, a drug, are spherical, have a smooth surface, and an average diameter of 10-100 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 meeting the claimed ranges (see table 1 of the instant specification).
Regarding claim 9, the limitation appears to be intended use for the same reasons discussed above and appears to be capable of being formulated for sustained release for 3 months, as taught by Kim ‘583. Purely arguendo, if not intended use, it would have been obvious to formulate the microparticles for sustained release of the active for 3 months, as motivated by Kim ‘583, depending on desired therapeutic activity and desired treatments.
Regarding the additional limitations of claims 1-3, 5, 6, and 8-11, the limitations are obvious for the same reasons discussed above as applied to each and every claimed limitation.
Claims 1, 3, 5, 6, 10, and 11, are 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”), Lee et al (WO 2020130585 A1, hereinafter "Lee"), Srinivas et al (US 20080226742 A1, hereinafter “Srinivas”).
The references 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, Kim ‘677, and Lee, 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).
Response to Arguments
Applicants assert that even if Srinivas teaches broad surface area ranges, Srinivas does not teach the presently claimed combination of polylactide with leuprorelin or deslorelin, particle size distribution width of 25 microns or less, span value of 0.5 or less, and the specified sustained-release microparticle profiles. Applicants assert a broad disclosure of surface area in an unrelated controlled-release polymeric microparticle context does not supply the missing teaching of the claimed leuprorelin/deslorelin microparticle combinations. Applicants assert the claimed specific surface area is not claimed in isolation, rather it is claimed together with a defined particle size distribution with and span value.
Respectfully, this argument is not persuasive. Like the combination above, Srinivas is directed to polymeric microparticles for the delivery of an active agent with particle sizes overlapping the claimed ranges, where these microparticles were known to be formulated with varying specific surface areas ranging from 0.01-500 m2g. It would have been obvious for the skilled artisan to modify the microparticles made obvious above 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, to allow for better control over drug release. As the property of specific surface are is understood to be tunable to a desired outcome, one of ordinary skill in the art would have been motivated to adjust the specific surface area in order to achieve desired and optimal microparticles capable of excellent therapeutic benefit, where these properties allow for better control over the drug release.
Claims 1-3, 5, 6, and 8-11, are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al (WO 2019078583 A1, hereinafter “Kim ‘583”), in view of Jin et al (US 20140314853 A1, hereinafter "Jin"), Kim et al (US 20180133677 A1, hereinafter “Kim ‘677”), Lee et al (WO 2020130585 A1, hereinafter "Lee"), Srinivas et al (US 20080226742 A1, hereinafter “Srinivas”).
The references 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 is discussed above.
It would have been obvious to formulate the microparticles made obvious above in view of Kim ‘583, Jin, Kim ‘677, and Lee, 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, and 8-11, are 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”), Jin et al (US 20140314853 A1, hereinafter "Jin"), Kim et al (US 20180133677 A1, hereinafter “Kim ‘677”), Lee et al (WO 2020130585 A1, hereinafter "Lee"), 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 (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, the span value, nor the surface area per unit mass of claim 1, the drugs as instantly claimed.
The references are discussed above.
It would have been obvious to modify ‘686 based on the teachings above.
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).
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).
It would have been obvious to formulate the microparticles with known Span values suitable for sustained release microparticles comprising a biodegradable polymer and a drug, such as those taught by Lee above and for the same reasons.
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 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, including leuprorelin or deslorelin, for the same reasons discussed above.
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:
Copending Application No. 18/285,002, while the claims disclose sustained release microparticles comprising polylactide and a drug, the claims do not disclose the drugs instantly claimed, the average diameter, the particle size distribution, the span value, nor the specific surface area instantly claimed. It would have been obvious to modify the claim of ‘002 for the same reasons discussed above.
Response to Arguments
Applicants assert that the newly amended claims are limited to polylactide, a drug selected from leuprorelin and deslorelin, and further recites a particle size distribution width of 25 microns or less and a Span value of 0.5 or less. Applicants assert the cited claims do not recite the presently claimed microparticle combinations.
Examiner disagrees. The double patent rejections have been updated to reflect the newly amended claims, and are obvious for the reasons discussed above.
Claims 1-3, 5, 6, and 8-11, are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending Application No. 18/284,981 (reference application), hereinafter referred to as ‘981, in view of Kim et al (WO 2019078583 A1, hereinafter “Kim ‘583”), Kim et al (US 20180133677 A1, hereinafter “Kim ‘677”), Lee et al (WO 2020130585 A1, hereinafter "Lee"), 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 ‘981 disclose microparticles comprising leuprorelin or deslorelin and polylactide. The particles are spherical and have a smooth surface.
The claims of ‘981 differ insofar as they do not disclose the average diameter, the particle size distribution, the span value, nor the specific surface area instantly claimed.
It would have been obvious to modify the claim of ‘981 for the same reasons discussed above.
It would have been obvious to formulate the microparticles with an diameter of 10-100 microns, as taught by Lee 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).
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).
It would have been obvious to formulate the microparticles with known Span values suitable for sustained release microparticles comprising a biodegradable polymer and a drug, such as those taught by Lee above and for the same reasons.
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).
Purely arguendo, if the specific surface area is not inherent, it would have been obvious to formulate 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.
Regarding sustained release over a desired period, it would have been obvious to formulate the microparticles for sustained release over 6 months, 1 week to 3 months, as taught by Kim ‘583 and Lee above.
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 the newly amended claims are limited to polylactide, a drug selected from leuprorelin and deslorelin, and further recites a particle size distribution width of 25 microns or less and a Span value of 0.5 or less. Applicants assert the cited claims do not recite the presently claimed microparticle combinations.
Examiner disagrees. The double patent rejection has been updated to reflect the newly amended claims, and are obvious for the reasons discussed above.
Claims 1-3, 5, 6, and 8-11, are 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, in view of Jin et al (US 20140314853 A1, hereinafter "Jin"), and Lee et al (WO 2020130585 A1, hereinafter "Lee"). 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 Span value of 0.35 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 is selected from polylactide (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).
The claims of ‘155 do not disclose leuprorelin or deslorelin, nor the average diameter as instantly claimed.
It would have been obvious to modify the claims of ‘155 by including other known active agents suitable for sustained release microparticles comprising a biodegradable polymer, including leuprorelin or deslorelin, as taught by Jin or Lee above, depending on desired therapeutic activity.
It would have been obvious to formulate the microparticles with known average diameters suitable for sustained release microparticles comprising a drug and a biodegradable polymer, such as 10-100 microns, as taught by Lee.
Regarding the 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).
It would have been obvious to formulate the microparticles with a span value of 0.35 or less, as disclosed by the claims of ‘155, falling within the claimed range.
It would have been obvious to formulate the microparticles with a specific surface area per unit mass as instantly claimed, as disclosed by the claims of ‘155.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicants have not provided argument with respect to the nonstatutory double patenting rejection over the claims of ‘155.
The double patent rejection over the claims of ‘155 has been updated to reflect the newly amended claims, and are obvious for the reasons discussed above.
Claims 1-3, 5, 6, and 8-11, are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending Application No. 18/767,008 (reference application), hereinafter ‘008, in view of Jin et al (US 20140314853 A1, hereinafter "Jin"), Kim et al (US 20180133677 A1, hereinafter “Kim ‘677”), Lee et al (WO 2020130585 A1, hereinafter "Lee"), 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 ‘008 disclose sustained release microparticles comprising deslorelin and a biodegradable polymer, having an average diameter of 65-100 microns. The biodegradable polymer comprises polylactide.
The claims of ‘008 do not disclose the particle size distribution, the span, the specific surface area, leuprorelin, the sustained release times as instantly claimed, nor specifically wherein the particles are smooth/spherical.
It would have been obvious to modify the claims by including other known active agents suitable for sustained release microparticles comprising a biodegradable polymer, including leuprorelin, as taught by Jin above, depending on desired therapeutic activity.
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).
It would have been obvious to formulate the microparticles with known Span values suitable for sustained release microparticles comprising a biodegradable polymer and a drug, such as those taught by Lee above and for the same reasons.
It would have been obvious to formulate 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.
Regarding sustained release over a desired period, it would have been obvious to formulate the microparticles for sustained release over 6 months, 1 week to 3 months, as taught by Lee above.
It would have been obvious to formulate the microparticles that are spherical and with a smooth surface, where these were known to be suitable for sustained release microparticles containing an active agent and polylactide, as taught by Kim ‘677.
The following are also rejected for the same reasons for comprising microparticles comprising an active agent and a biodegradable polymer:
Copending application no. 18/170,602, while the claims disclose a method comprising microparticles comprising deslorelin and a biodegradable polymer, the claims do not disclose the particle size distribution, the span, the specific surface area, leuprorelin, the sustained release times as instantly claimed, nor specifically wherein the particles are smooth/spherical. It would have been obvious to modify the claims of ‘602 for the same reasons discussed above.
Claims 1-3, 5, 6, and 8-11, are 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”), Jin et al (US 20140314853 A1, hereinafter "Jin"), Kim et al (US 20180133677 A1, hereinafter “Kim ‘677”), Lee et al (WO 2020130585 A1, hereinafter "Lee"), 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, and are capable of continuous drug release for 1-3 months without initial excess release (claim 1). The biodegradable polymer is selected from polylactide.
‘508 does not disclose wherein the drugs are leuprorelin or deslorelin, the particle size distribution, the span value, the specific surface area instantly claimed, the release pattern as instantly claimed.
It would have been obvious to select from drugs that are taught to be suitable for sustained release microparticles, such as leuprorelin or deslorelin, for the same reasons discussed above by Jin and Lee.
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).
It would have been obvious to formulate the microparticles with known Span values suitable for sustained release microparticles comprising a biodegradable polymer and a drug, such as those taught by Lee above and for the same reasons.
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.
Regarding sustained release over a desired period, it would have been obvious to formulate the microparticles for sustained release over 6 months, 1 week to 3 months, as taught by Kim ‘583 and Lee above.
The following also stand rejected for comprising sustained release microparticles comprising a biodegradable polymer and a drug, based on the modifications discussed above:
U.S. Patent No. 11931461 B2, while disclosing microparticles comprising a drug and a biodegradable polymer (PLGA), having an average diameter of 80-130 microns, and having sustained release over 3-6 months, the claims do not disclose the drugs instantly claimed, polylactide specifically, the average diameter of claims 8 and 10, the particle size distribution, the span value, nor the specific surface area instantly claimed. It would have been obvious to modify the claim of ‘461 for the same reasons discussed above.
U.S. Patent No. 11504688 B2, while disclosing extended release microparticles comprising a drug and a biodegradable polymer, the claims do not disclose the drugs instantly claimed, polylactide specifically, the average diameter, the particle size distribution, the span value, nor the specific surface area instantly claimed. It would have been obvious to modify the claim of ‘688 for the same reasons discussed above.
U.S. Patent No. 11344624 B2, while disclosing microparticles comprising polylactide and finasteride (drug), wherein the microparticles have an average particle diameter of 20-70 microns, the claims do not disclose the drugs instantly claimed, the average diameter of claims 8 and 10, the particle size distribution, the span value, nor the specific surface area instantly claimed. It would have been obvious to modify the claim of ‘624 for the same reasons discussed above.
Response to Arguments
Applicants assert that the newly amended claims are limited to polylactide, a drug selected from leuprorelin and deslorelin, and further recites a particle size distribution width of 25 microns or less and a Span value of 0.5 or less. Applicants assert the cited claims do not recite the presently claimed microparticle combinations.
Examiner disagrees. In view of Applicants amendments to the instant claims, the nonstatutory double patenting rejections have been updated and appears to make obvious the missing features.
Claims 1-3, 5, 6, and 8-11, are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent No. 12251419 B2, hereinafter referred to as ‘419, in view of Jin et al (US 20140314853 A1, hereinafter "Jin"), Kim et al (US 20180133677 A1, hereinafter “Kim ‘677”), Lee et al (WO 2020130585 A1, hereinafter "Lee"), 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 ‘419 disclose a method comprising sustained release microparticles containing deslorelin and a biodegradable polymer, wherein the biodegradable polymer is selected from polylactide. The particles have an average diameter of 25-140 microns.
The claims of ‘419 do not disclose the particle size distribution, the span, the specific surface area, leuprorelin, the sustained release times as instantly claimed, nor specifically wherein the particles are smooth/spherical.
It would have been obvious to modify the claims by including other known active agents suitable for sustained release microparticles comprising a biodegradable polymer, including leuprorelin, as taught by Jin above, depending on desired therapeutic activity.
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).
It would have been obvious to formulate the microparticles with known Span values suitable for sustained release microparticles comprising a biodegradable polymer and a drug, such as those taught by Lee above and for the same reasons.
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).
Purely arguendo, if the specific surface area is not inherent, it would have been obvious to formulate 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.
Regarding sustained release over a desired period, it would have been obvious to formulate the microparticles for sustained release over 6 months, 1 week to 3 months, as taught by Lee above.
It would have been obvious to formulate the microparticles that are spherical and with a smooth surface, where these were known to be suitable for sustained release microparticles containing an active agent and polylactide, as taught by Kim ‘677.
Conclusion
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/JOSHUA A ATKINSON/Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
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