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 .
Claims 1-4, 6, 8-11, 14-17, 21-23, 25-26, 28-29, 31, 38-42, 44, and 115-118 are pending in the application.
DETAILED ACTION
Election/Restriction
This application contains claims directed to the following patentably distinct species: 1) at least one drug; 2) first drug, as indicated in generic claim 21 and 3) second drug, as indicated in generic claim 21. The species are independent or distinct because the drugs belong to different drug classes that will require a different search of the prior art. Regarding the 1) at least one drug, the drugs claimed include prostamide analog, prostaglandin analog, a beta-adrenergic blocker or cyclosporin. Regarding the 2) first drug, as indicated in generic claim 21, the first drug can be any drug. Regarding the 3) second drug, as indicated in generic claim 21, the second drug includes a carbonic anhydrase inhibitor, a prostaglandin analog, a prostamide analog, or a rho-kinase inhibitor. The search of the different drug species will require different fields of search. In addition, these species are not obvious variants of each other based on the current record.
Applicant is required under 35 U.S.C. 121 to elect a single disclosed species, or a single grouping of patentably indistinct species, for prosecution on the merits to which the claims shall be restricted if no generic claim is finally held to be allowable. Currently, 1-4, 6, 8-9, 14-17, 21, 39-42, 44, 115-118 are generic.
There is a serious search and/or examination burden for the patentably distinct species as set forth above because at least the following reason(s) apply: a) the species have acquired a separate status in the art in view of their different classification; (b) the species have acquired a separate status in the art due to their recognized divergent subject matter; (c) the species require a different field of search (for example, searching different classes/subclasses or electronic resources, or employing different search queries); (d) the prior art applicable to one species would not likely be applicable to another invention; (e) the species are likely to raise different non-prior art issues under 35 U.S.C. 101 and/or 35 U.S.C. 112, first paragraph.
Applicant is advised that the reply to this requirement to be complete must include (i) an election of a species to be examined even though the requirement may be traversed (37 CFR 1.143) and (ii) identification of the claims encompassing the elected species or grouping of patentably indistinct species, including any claims subsequently added. An argument that a claim is allowable or that all claims are generic is considered nonresponsive unless accompanied by an election.
The election may be made with or without traverse. To preserve a right to petition, the election must be made with traverse. If the reply does not distinctly and specifically point out supposed errors in the election of species requirement, the election shall be treated as an election without traverse. Traversal must be presented at the time of election in order to be considered timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are added after the election, applicant must indicate which of these claims are readable on the elected species or grouping of patentably indistinct species.
Should applicant traverse on the ground that the species, or groupings of patentably indistinct species from which election is required, are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing them to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the species unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other species.
Upon the allowance of a generic claim, applicant will be entitled to consideration of claims to additional species which depend from or otherwise require all the limitations of an allowable generic claim as provided by 37 CFR 1.141.
During a telephone conversation with Kenichi Hartman on December 22, 2025 a provisional election was made without traverse to prosecute the species of 1) carbonic anhydrase inhibitor as the at least one drug; 2) beta-adrenergic blocker as the first drug, and 3) carbonic anhydrase inhibitor as the second drug. Affirmation of this election must be made by applicant in replying to this Office action. Claims 10, 28, 29, and 31 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Claims 1-4, 6, 8-11, 14-17, 21-23, 25-26, 28-29, 31, 38-42, 44, and 115-118 are pending in the application. Claims 10, 28, 29, and 31 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention. Claims 1-4, 6, 8-9, 11, 14-17, 21-23, 25-26, 38-42, 44, and 115-118 will presently be examined to the extent they read on the elected subject matter of record.
Priority
This application claims benefit to U.S. Provisional Application No. 63/428,389 filed November 28, 2022.
Information Disclosure Statement
Receipt of Information Disclosure Statement filed February 21, 2024 is acknowledged.
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.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 2, 3, 4, 6, 9, 11, 16, and 39 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Chang (US 2009/0264813). Chang cited by Applicant on the IDS dated 2/21/2024.
Chang discloses an apparatus and methods useful for placing drug delivery implants, for example, substantially biodegradable drug delivery implants, into an eye without the need for a liquid carrier medium and without causing any substantial breakage or other damage to the implant (page 1, paragraph 9). Chang discloses the apparatus comprises a cannula having a liquid free lumen extending therethrough, the lumen having a length and a diameter and being configured to receive an ocular implant comprising a plurality of substantially uniformly sized liquid free, or dry, particles arranged in a one-by-one (synonymously, in a single file manner) array along the length of the lumen (page 1 paragraph 10).
Regarding claims 1, 2, 3, 4, 6, 9, 11, 16, and 39, Chang discloses in Example 3, Microspheres (plurality microparticles/microspheres) are made with 80% poly-d, l-lactide-co-glycolide (Boehringer-Ingleheim 752H)(poly(lactic-co-glycolic acid) and 20% cyclosporine having a uniform diameter of 280+/-.5 µm (diameter between 1µm and about 500 µm). Each microsphere has about 0.0028 mg cyclosporine (drug-eluting matrix comprising bio-erodible polymer and at least one drug, cyclosporin) . An applicator with an extra thin-walled 27-g needle (i.d.=0.29 mm) can be filled with about 100 microspheres to reach a total drug content of about 0.27 mg. Total length of loaded microspheres in the needle is 28 mm, compared to 19 mm of a thermally extruded rod with a 280 µm diameter and 0.28 mg cyclosporine. The microspheres are be injected subconjunctivally and the drug is released over a period of three months (implanted subconjunctival space, deliver at least 1 month).
Chang meets all the limitations of the claims and thereby anticipates the claims.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-4, 6, 8-9, 11, 14-16, 21-23, 25-26, 38, 39, 40-42, 44, and 115-118 are rejected under 35 U.S.C. 103 as being unpatentable over Chang (US 2009/0264813) in view of Yang et al. (US 2020/0031783). Chang cited by Applicant on the IDS dated 2/21/2024.
Applicant’s Invention
Applicant claims a method of treating a condition of an eye of a subject, the method comprising implanting a dry implant formulation in the eye of the subject without a carrier, the dry implant formulation comprising a plurality of drug-eluting microparticle implants, wherein at least one drug is delivered from the plurality of drug-eluting microparticle implants to the eye to reduce a symptom associated with the condition of the eye.
Determination of the scope of the content of the prior art
(MPEP 2141.01)
The teachings of Chang with respect to the 35 U.S.C. 103 rejection is hereby incorporated and are therefore applied in the instant rejection as discussed above.
Regarding claims 1 and 2, Chang teaches the plurality of particles comprises compositions including at least one therapeutic component effective to provide a therapeutic effect when released into an eye, and a biodegradable component, a non-biodegradable component, and combinations thereof.
Regarding claim 3, Chang teaches the particles which make up the implant comprise a composition comprising a therapeutic component and a polymeric component for controlling release of the therapeutic component from the particle (page 4, paragraph 49).
Regarding claim 4, Chang teaches polymers of D-lactic acid, L-lactic acid, racemic lactic acid, glycolic acid, polycaprolactone, and combinations thereof (page 4, paragraph 50). Chang teaches copolymers of glycolic and lactic acid are of particular interest, where the rate of biodegradation is controlled by the ratio of glycolic to lactic acid. The % of polylactic acid in the polylactic acid polyglycolic acid (PLGA) copolymer can be 0-100%...more preferably about 35-65% (page 6, paragraph 67).
Regarding claims 8 and 118, Chang teaches an anterior ocular condition can include a disease, ailment or condition, such as dry eye syndromes. Glaucoma can also be considered to be an anterior ocular condition because a clinical goal of glaucoma treatment can be to reduce a hypertension of aqueous fluid in the anterior chamber of the eye (i.e. reduce intraocular pressure) (page 3, paragraph 40).
Regarding claims 14 and 15, Chang teaches the implant 16 delivers the agent to the vitreous in an amount sufficient to reach a concentration equivalent to at least about 0.3 µg/ml,…or at least about 2.0 µg/ml dexamethasone within about 4 hours, or within about 6 hours, or within about 8 hours, or within about 10 hours, or within about 24 hours (page 5 paragraph 63). 2 µg falls within the range of 1 ng/day and about 50 µg per day. 2 µg is equivalent to 2000 ng.
Regarding claims 9, 116, and 117, Chang teaches in one embodiment, more than one implant 16 may be sequentially implanted into the vitreous, for example in different locations in the vitreous, in order to maintain therapeutic component or drug concentrations for even longer periods (page 6, paragraph 65).
Regarding claim 21, Chang teaches a single implant may comprise one or more particles comprising a first therapeutic component, and one or more other particles comprising a second therapeutic component that is different from the first therapeutic component (page 6, paragraph 69).
Regarding claims 21 and 115, Chang teaches the microparticles provide the ability to load different drugs into different microspheres and/or individually design the drug release rate for each microsphere by varying polymer composition, drug content, or the processing conditions (page 7, paragraph 85).
Regarding claims 11, 22, and 23, Chang teaches anti-glaucoma drugs, such as the beta-blockers, such as timolol maleate (page 5, paragraph 58).
Regarding claims 41 and 42, Chang teaches calcium alginate, and functionalized celluloses (page 4, paragraph 51).
Regarding claim 44, Chang teaches the implant is structured to have a lifetime at least equal to the desired period of therapeutic component administration in the eye and may have lifetimes of about 5 to about 10 times the desired period of administration (page 4-5, paragraph 55).
Chang teaches implants that are compatible with loading and ejection from apparatus can be formed by a number of known methods, including heat press methods and the like. Particular methods used can be chosen, and technique parameters varied, based on desired implant size and drug release characteristics.
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02)
Chang does not specifically disclose the second drug is a carbonic anhydrase inhibitor, as claimed in claims 25 and 26; an example wherein the first drug is timolol and the second drug is dorzolamide or brinzolamide, and wherein the dry implant formulation is implanted in sub-Tenon’s space; or the plurality of the drug-eluting microspheres have been heated above the glass transition temperature of the bio-erodible polymer. It is for this reason Yang et al. is added as a secondary reference.
Regarding claims 25, 26, and 38, Yang et al. teach timolol-Dorzolamide bi-functional prodrugs in polymeric microspheres and concurrent dual drug release. Timolol-Dorzolamide bi-functional prodrugs were encapsulated in polymeric microspheres (page 266, paragraph 1260).
Yang et al. teach parent timolol and Dorzolamide prodrugs were released concurrently from the bi-functional prodrug-loaded (page 266, paragraph 1262).
Yang et al. teach FIGS. 49A and 49B are graphs comparing the percent release of free Timolol and Dorzolamide linked with PLA moieties that is released from microparticles encapsulating Timolol-Dorzolamide prodrug (page 127, paragraph 705).
Yang et al. teach FIG. 50 is a graph of measuring the percent release of free Timolol and Dorzolamide linked with PLA moieties that is released from microparticles encapsulating Timolol-Dorzolamide prodrug (page 125, paragraph 706).
Yang et al. teach the prodrugs treat medical disorders, for example glaucoma (Abstract).
Regarding claim 38, Yang et al. teach the formulations are administered sub-tenon (page 7, paragraph 118; page 490, claim 46).
Finding a prima facie obviousness
Rationale and Motivation (MPEP 2142-2143)
It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to combine the teachings of Chang and Yang et al. and use a carbonic anhydrase inhibitor in the composition and as the second drug. Chang teaches the plurality of particles comprises compositions including at least one therapeutic component effective to provide a therapeutic effect when released into an eye, and a biodegradable component, a non-biodegradable component, and combinations thereof. Chang teaches a single implant may comprise one or more particles comprising a first therapeutic component, and one or more other particles comprising a second therapeutic component that is different from the first therapeutic component. Chang teaches anti-glaucoma drugs, such as the beta-blockers, such as timolol maleate, are used in the microparticles. One of ordinary skill in the art would have been motivated to use a carbonic anhydrase inhibitor as the second drug because microparticle compositions comprising timolol and dorzolamide are known in the art as taught by Yang et al. Yang et al. teach timolol-Dorzolamide bi-functional prodrugs in polymeric microspheres and concurrent dual drug release. It would have been obvious to one of ordinary skill in the art to use the teachings of the prior art references to add a known second drug that is formulated as a microparticle, with a reasonable expectation of success, as a person with ordinary skill has good reason to pursue known options within his or technical grasp. Note: MPEP 2141 [R-6] KSR International CO. v. Teleflex lnc. 82 USPQ 2d 1385 (Supreme Court 2007). In addition, both timolol and dorzolamide, are used to treat glaucoma. In view of In re Kerkhoven, 205 USPQ 1069 (C.C.P.A. 1980), it is prima facie obvious to combine two or more compositions each of which is taught by prior art to be useful for the same purpose in order to form a third composition that is to be used for the very same purpose. The idea of combining them flows logically from their having been individually taught in prior art, thus claims that requires no more than mixing together two or three conventional drugs that are known to treat glaucoma set forth prima facie obvious subject matter.
It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to combine the teachings of Chang and Yang et al. and implant the formulation in the sub-Tenon’s space. Chang teaches the plurality of particles comprises compositions including at least one therapeutic component effective to provide a therapeutic effect when released into an eye, and a biodegradable component, a non-biodegradable component, and combinations thereof. Chang teaches a single implant may comprise one or more particles comprising a first therapeutic component, and one or more other particles comprising a second therapeutic component that is different from the first therapeutic component. Chang teaches the microparticles are used to treat various ocular conditions in different parts of the eye, such as the anterior ocular, posterior ocular, sclera, and subconjunctival. One of ordinary skill in the art would have been motivated to inject the microparticles in various parts of the eye, such as the sub-tenon, as it is a known to inject medications in the sub-tenon, as taught by Yang et al. Yang et al. teach the formulations are administered sub-tenon. It would have been obvious to one of ordinary skill in the art to use the teachings of the prior art references to administer the microparticles in techniques taught by the prior art, with a reasonable expectation of success, as a person with ordinary skill has good reason to pursue known options within his or technical grasp. Note: MPEP 2141 [R-6] KSR International CO. v. Teleflex lnc. 82 USPQ 2d 1385 (Supreme Court 2007).
Regarding the limitation wherein the plurality of the drug-eluting microspheres have been heated above the glass transition temperature of the bio-erodible polymer, Chang teaches implants that are compatible with loading and ejection from apparatus can be formed by a number of known methods, including heat press methods and the like. One of ordinary skill in the art would have been motivated to use known techniques, including a heat press method that would heat the microspheres above the glass transition temperature because particular methods used can be chosen, and technique parameters varied, based on desired implant size and drug release characteristics. The adjustment of particular conventional working conditions is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan. Accordingly, this type of modification would have been well within the purview of the skilled artisan and no more than an effort to optimize results.
Therefore, the claimed invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Chang (US 2009/0264813) in view of Yang et al. (US 2020/0031783) as applied to claims 1-4, 6, 8-9, 11, 14-16, 21-23, 25-26, 38, 39, 40-42, 44, and 115-118 above, and further in view of Xu et al. (US 2011/0104069).
Applicant’s Invention
Applicant claims a method of treating a condition of an eye of a subject, the method comprising implanting a dry implant formulation in the eye of the subject without a carrier, the dry implant formulation comprising a plurality of drug-eluting microparticle implants, wherein at least one drug is delivered from the plurality of drug-eluting microparticle implants to the eye to reduce a symptom associated with the condition of the eye.
Determination of the scope of the content of the prior art
(MPEP 2141.01)
The teachings of Chang and Yang et al. with respect to the 35 U.S.C. 103 rejection is hereby incorporated and are therefore applied in the instant rejection as discussed above.
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02)
Chang and Yang et al. do not specifically disclose at least a subset of the plurality of the microparticle implants comprises an imaging agent. It is for this reason Xu et al. is added as a secondary reference.
Regarding claim 17, Xu et al. teach methods of using microparticles and nanoparticles for treatment of ocular disorders. The provided methods comprise (a) administering to a subject a composition comprising at least one of the provided particles, said particles comprising at least one ocular targeting agent; (b) pausing for a pre-determined period of time to allow the administered particles to migrate to the ocular target; (c) optionally, confirming migration to the ocular target using one or more ocular imaging tools; and (d) optionally, administering sufficient energy from at least one energy source to cause the migrated particles to expand (page 1, paragraph 7). Xu et al. teach the provided particles and methods allow a clinician to selectably control the multiple functions of the particles to deliver therapeutic agents in a controllable process. Delivery of therapeutic agents may be monitored by ocular imaging tools before, during, or after delivery of the therapeutic agents, thereby providing a clinician with additional control over the particles and the delivery process.
Finding a prima facie obviousness
Rationale and Motivation (MPEP 2142-2143)
It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to combine the teachings of Chang, Yang et al., and Xu et al. and add an imaging agent to a subset of the plurality of microparticle implants. Chang teaches the plurality of particles comprises compositions including at least one therapeutic component effective to provide a therapeutic effect when released into an eye, and a biodegradable component, a non-biodegradable component, and combinations thereof. Chang teaches a single implant may comprise one or more particles comprising a first therapeutic component, and one or more other particles comprising a second therapeutic component that is different from the first therapeutic component. Xu et al. teach particles and methods that have similar particles taught by Chang. As such, one of ordinary skill in the art would have been motivated to add an imaging agent to the microparticle implants taught by Chang, as modified by Yang et al., to be monitored by ocular imaging tools before, during, or after delivery of the therapeutic agents, thereby providing a clinician with additional control over the particles and the delivery process such as selectably controlling the multiple functions of the particles to deliver therapeutic agents in a controllable process, with a reasonable expectation of success.
Therefore, the claimed invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Andriae M Holt whose telephone number is (571)272-9328. The examiner can normally be reached Monday-Friday, 8:00 am-4:30 pm EST.
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/ANDRIAE M HOLT/ Examiner, Art Unit 1614
/ALI SOROUSH/ Supervisory Patent Examiner, Art Unit 1614