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 .
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-18, 20, 21, 23-27, 29-32, 38, and 39, in the reply filed on 09/17/2025 is acknowledged. The traversal is on the ground(s) that the search of groups I and III would not place undue burden on the Patent Office. This is not found persuasive because a search burden is not a requirement under 371 practice.
The requirement is still deemed proper and is therefore made FINAL.
Applicant’s provisional election of poly(lactic-co-glycolic acid) (PLGA) as the single biocompatible polymer, magnesium hydroxide as the single release modifier, and nanoparticles as the single pharmaceutical form of claim 18, in the reply filed on 09/17/2025 is acknowledged.
Claims 16, 24, 25, 40-44, 49, and 51-56, are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention/species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 09/17/2025.
Claim Objections
Claims 4, 7, 14, 18, 20, 23, 29, 32, 38, and 39, are objected to because of the following informalities: following the claim number, the space additional space between the number and comma should be removed. Appropriate correction is required.
Claim 10 is objected to because of the following informalities: following the claim number, a comma is missing. Appropriate correction is required.
Claim 18 is also objected to because of the following informalities: the claim recites “…in the form of microparticles or nanoparticles or a combination thereof”, and the claim should read “…in the form of microparticles, nanoparticles or a combination thereof.” Appropriate correction is required.
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 7-15, 17 and 23, 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.
Claims 7 and 14 recite “selected from the group comprising,” which is indefinite because it is unclear what other alternatives are intended to be encompassed by the claim.
Claim 23 recites a percent porosity for the nanoparticles, however, it is unclear whether the percent porosity is a percent by volume, percent by weight, etc., leading to a lack of clarity in how the porosity is defined. For purposes of examination, the percent porosity is interpreted consistent with the instant specification, where percent porosity is defined as the as the ratio of the total pore volume to the apparent volume of the nanoparticles (see ¶ 151 of the instant specification).
Claims 8-13, 15, and 17, are also rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph for depending upon their respective base claims.
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, 7-14, 17, 18, 23, 26, and 39, are rejected under 35 U.S.C. 103 as being unpatentable over Dadey et al (US 20060210604 A1, cited on IDS dated 06/16/2025).
Dadey et al teach flowable controlled release formulations comprising a biocompatible polymer and a biological agent, wherein the composition is suitable for ocular delivery (abs, claim 1). The biological agent is selected from griseofulvin, etc. (¶ 49, claim 38). The compositions can be formulated into a 1, 2, 3, or 6 months delivery system of biological agent (¶ 145). The controlled-release formulation can be formulated with linear, first order, or zero order kinetics, and can be formulated with little or no drug burst (¶ 154). The biocompatible polymer is selected from poly(lactide-co-glycolide), with an average molecular weight of about 15,000 to about 45,000 (¶¶ 219, 240, 242, claims 9, 20). By an appropriate choice of the polymer molecular weight in combination with an effective amount of the release rate modification agent, the release rate and extent of release of a bioactive agent from the implant matrix may be varied (¶ 170). The poly(lactide-co-glycolide) can be 50/50 or 75/25 (¶¶ 217, 242). The biocompatible polymer can be up to about 80 wt% of the composition (¶ 218). The formulations can comprise release-rate modifiers up to 60 wt% of the composition, preferably about 0.5-15 wt%, in order to increase or retard the rate of release (¶¶ 167-168). Release-rate modifiers include polyethylene glycol, etc. (¶ 173). Pore forming agents can also be included, such as polyvinylpyrrolidone, sucrose, etc., where the size and extent of the pores can be varied over a wide range by changing the molecular weight and percentage of pore-forming additive (¶ 177). The formulation may be in the form of a nanoparticle (claim 56). The formulations will have a porosity in the range of about 5-95% as measured by the percent solid of the volume of the solid, which is in part governed by the degree of water solubility of the solvent and thermoplastic polymer (¶ 198). The control of the degree of porosity is beneficial for generating different kinds of devices (¶ 198). The biological active can be present up to about 70 wt%, up to about 40 wt%, up to about 20 wt%, etc. (¶ 148).
Dadey et al does not specifically teach a particular embodiment as instantly claimed comprising griseofulvin for long-term release for a period of about 1 month to about 6 months.
Regarding claims 1-3, it would have been obvious to formulate a formulation that can be used for ocular administration comprising griseofulvin for long-term release of 1 months to 6 months, as taught by Dadey et al.
Regarding claims 7 and 8, it would have been obvious to select from poly(lactide-co-glycolide) (i.e., poly(lactic acid-co-glycolic acid)) as the biocompatible polymer, as taught by Dadey et al.
Regarding claims 9 and 10, it would have been obvious to select a poly(lactide-co-glycolide) with an average molecular weight ranging from about 15,000 to about 45,000, as taught by Dadey et al, where it was known that modifying molecular weight is a method of modifying bioactive agent release rate, in order to optimize the formulations for desired release of griseofulvin.
Regarding claims 11 and 12, it would have been obvious to select from poly(lactide-co-glycolide) polymers with a molar ratio of lactic acid to glycolic acid of 50/50 or 75/25, as taught by Dadey et al. 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 13, it would have been obvious to include the biocompatible polymer in amounts up to about 80 wt% of the composition, as taught by Dadey et al. 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 14, it would have been obvious to further include a release rate modifier, such as polyethylene glycol, or pore forming agents such as polyvinylpyrrolidone or sucrose, which would also be expected to modify the release of the active agent. While not the provisionally elected release rate modifier, the reference will be used to its fullest extent as applied to the presented claims.
Regarding claim 17, it would have been obvious to include the release rate modifier up to about 80 wt%, preferably 0.5-15 wt%, depending on the desired release rate. Further, it would have been well within the relative skills of the skilled artisan to determine the optimal amount of release rate modifier for long-term release of griseofulvin. 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(II)(A).
Regarding claim 18, it would have been obvious to formulate the formulation made obvious above in the form of nanoparticles, as taught by Dadey et al.
Regarding claim 23, it would have been obvious to formulate the formulation made obvious above with a porosity ranging from 5-95%, as taught by Dadey et al. Further, where it is taught that porosity can vary, it would have been obvious to for the skilled artisan to routinely optimize the porosity of the formulations, where the skilled artisan would recognize that the porosity effect both the strength and release rate/degradation of the formulations, in order to achieve desired release and structural properties. See MPEP 2144(II)(A).
Regarding claim 26, it would have been obvious to formulate the formulations of Dadey et al with griseofulvin in an amount such as up to about 40 wt% or up to about 20 wt%, with a biocompatible polymer at a concentration of up to about 80 wt% of the composition, and a release modifier at a concentration of about up to 60 wt%, preferably about 0.5-15 wt%, as taught by Dadey et al 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).
Regarding claim 39, where the amount of griseofulvin can be up to about 70 wt%, up to about 40 wt%, up to about 20 wt%, etc., and the amount of biocompatible polymer can be up to about 80 wt% of the composition, as taught by Dadey et al above, if for example 20 wt% of griseofulvin was formulated with 80 wt% biocompatible polymer, the resulting weight ratio of griseofulvin to biocompatible polymer would be 1:4, falling within the claimed ranges. 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).
Claims 14, 15, 17, 27, and 29-31, are rejected under 35 U.S.C. 103 as being unpatentable over Dadey et al (US 20060210604 A1, cited on IDS dated 06/16/2025), as applied to claims 1-3, 7-13, 18, 23, 26, and 39 above, and further in view of Kang et al (Biomat., 2002, vol. 23, issue 1, pp. 239-245), as evidenced by PubChem (Magnesium Hydroxide, retrieved 2025).
Dadey et al are discussed above and further teach the release rate modification agents are preferably water-insoluble (¶ 171).
Dadey et al does not teach the inclusion of Applicants’ elected release modifier, magnesium hydroxide.
Kang et al teach controlled-release systems comprising poly(lactide-co-glycolide) (PLGA) for the release of an active agent, where it was known that the inclusion of magnesium hydroxide influences the release rate and stability of the active agent from the PLGA implants (abs, 4.2, fig. 3). The inclusion of magnesium hydroxide acts to reverse the effect from the acidic microenvironment accompanying PLGA degradation (intro 1st ¶). Magnesium hydroxide was included in the working embodiments in amounts of 3% and 6% (fig. 3). As evidenced by PubChem, magnesium hydroxide is water-insoluble (3.2.1). Kang et al further discloses release rates of bovine serum albumin (active agent) from PLGA millicylinders with a cumulative release shown in fig. 3A (fig. 3A).
Regarding claims 14 and 15, it would have been obvious to modify the formulation made obvious above by Dadey et al, by selecting from other known water-insoluble release modifiers that were known to effect the release rate of active agents from PLGA implants, such a magnesium hydroxide, as taught by Kang et al.
Regarding claims 17 and 27, it would have been obvious to include magnesium hydroxide in those amounts suitable for release modifiers, such as up to about 80 wt%, preferably 0.5-15 wt%, as taught by Dadey et al. Further, it would have been obvious to include magnesium hydroxide in the amount exemplified by the working embodiments of Kang et al, such as 3 wt% and 6 wt%, both having an effect on release rate. 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 claims 29 and 30, it would have been obvious to formulate the combination made obvious above long-term release of griseofulvin for 1 months to 3 months, as taught by Dadey et al. 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 31, where Dadey et al teach controlled release formulations than can release from about 1 month to about 6 months, and teaches the release profile can be linear, first order, or zero order, it would have been obvious for the skilled artisan to formulate the formulation made obvious by Dadey et al, with release profiles that were known to be suitable for PLGA formulations for prolonged release of an active agent, such as those of fig. 3A of Kang et al, which appear to show embodiments with a release rate falling within the ranges of claim 31. Further, it would have been well within the relative skills of the skilled artisan to routinely optimize the release profiles for griseofulvin specifically, depending on desired treatments, 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(II)(A).
Claims 4-6, 20, and 21, are rejected under 35 U.S.C. 103 as being unpatentable over Dadey et al (US 20060210604 A1, cited on IDS dated 06/16/2025), as applied to claims 1-3, 7-14, 17, 18, 23, 26, and 39 above, and further in view of Qiu et al (Molecular Pharm., 2019, vol. 16, issue 5, pp. 1958-1970).
Dadey et al are discussed above but do not explicitly disclose the release profile at 1 day, 10 days, and 30 days, nor the size of the nanoparticles as instantly claimed.
Qiu et al teach active agent loaded biodegradable PLGA nanoparticles for prolonged release suitable for ocular administration were it was known to formulate the PLGA nanoparticles with a size of around 250 nm (abs, results 1st ¶, table 2). Drug loading can be improved by increasing the particle size (pg. 1965 2nd col). The in vitro release profile of the PLGA nanoparticles are disclosed in figure 1B (fig. 1B).
Regarding claims 4-6, where Dadey et al teach controlled release formulations with a release profile from about 1 month to about 6 months, and teach the release rate can be linear, first order, or zero order, it would have been obvious for the skilled artisan to formulate the formulation made obvious by Dadey et al, with release profiles that were known to be suitable for PLGA nanoparticles for long term delivery of an active agent to the eye, such as those of fig. 1B of Qiu et al, which appears to show embodiments with release profiles overlapping those of instant claims 4- 6. Further, it would have been well within the relative skills of the skilled artisan to routinely optimize the release profile for griseofulvin specifically, depending on desired treatments, 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(II)(A).
Regarding claims 20 and 21, it would have been obvious to formulate the nanoparticles in the formulation made obvious above by Dadey et al, with known PLGA nanoparticle sizes suitable for prolonged release of an active for ocular administration, such as around 250 nm, as taught by Qiu et al, falling within the claimed ranges.
Claims 31 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Dadey et al (US 20060210604 A1, cited on IDS dated 06/16/2025) and Kang et al (Biomat., 2002, vol. 23, issue 1, pp. 239-245) as applied to claims 14, 15, 17, 27, and 29-30 above, and further in view of Qiu et al (Molecular Pharm., 2019, vol. 16, issue 5, pp. 1958-1970).
Dadey et al and Kang et al are discussed above.
The references, while teaching sustained release of an active agent from PLGA, do not specifically teach the release profile of instant claim 32. Additionally, while Kang et al appears to teach the release profile of instant claim 31, if somehow the release profile of Kang et al would not be expected to be suitable for ocular administration, the following also applies.
Qui et al are discussed above.
Regarding claims 31 and 32, where Dadey et al teach controlled release formulations than can release from about 1 month to about 6 months, and teaches the release rate can be linear, first order, or zero order, it would have been obvious for the skilled artisan to formulate the formulation made obvious by Dadey et al, with release profiles that were known to be suitable for PLGA nanoparticles for long term delivery of an active agent to the eye, such as those of fig. 1B of Qiu et al, which appears to show embodiments with release profiles overlapping those of claims 31 and 32. Further, it would have been well within the relative skills of the skilled artisan to routinely optimize the release profile for griseofulvin specifically, depending on desired treatments, 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(II)(A).
Claim 38 is rejected under 35 U.S.C. 103 as being unpatentable over Dadey et al (US 20060210604 A1, cited on IDS dated 06/16/2025), as applied to claims 1-3, 7-14, 17, 18, 23, 26, and 39 above, and further in view of Popov et al (US 20150125539 A1).
Dadey et al are discussed above but do not disclose the polydispersity index of the nanoparticles.
Popov et al teach nanoparticle compositions for ophthalmic applications for delivering pharmaceutical agents with prolonged release to the eye, wherein the nanoparticles may comprise PLGA and griseofulvin (abs, ¶¶ 118, 245). The nanoparticles may have a polydispersity index of less than or equal to about 1 (¶ 292).
Regarding claim 38, it would have been obvious to formulate the nanoparticles in the formulation made obvious above by Dadey et al, with a known polydispersity index suitable for PLGA nanoparticles for prolonged release of an active agent, such as less than or equal to about 1, as taught by Popov et al.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Bright et al (US 20130122097 A1) disclose compositions for the delivery of active agents comprising an active agent, a biodegradable polymer, and between about 1% to about 10 wt% of a release modifier (abs, ¶ 103). The compositions may be configured to deliver the antifungal agent for any suitable duration, such as at least about one month, etc. (¶ 94). Fig. 7 shows the cumulative release profile of one embodiment (fig. 7). The active agent is selected from griseofulvin, etc. (¶ 111).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSHUA A ATKINSON whose telephone number is (571)270-0877. The examiner can normally be reached M-F: 9:00 AM - 5:00 PM + Flex.
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/JOSHUA A ATKINSON/Examiner, Art Unit 1612
/MARIANNE C SEIDEL/Primary Examiner, Art Unit 1600