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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 10/14/2025 has been entered.
Status of the Claims
Claims 91, 97, 100, 102, 105-108, 111-118, 126 and 131-133 have been amended. Claims 1-90, 93, 101, 103, 104, 119-121 and 123-125 are cancelled. Claim 137 is newly added. Accordingly, claims 91, 92, 94-100, 102, 105-118, 122 and 126-137 remain pending in the application. 95, 113-118 and 134-136 stand withdrawn from further consideration, without traverse. Claims 91, 92, 94, 96-100, 102, 105-112, 122, 126-133 and 137 are currently under examination.
Withdrawn Rejections
Applicant’s amendment renders the rejection under 35 USC 103 over Robinson, Cordero-Coma, Andino and Kohn moot. Specifically, the references do not teach the new limitation, “at least 80% by weight of spherical particles”. Thus, said rejection has been withdrawn. However, after further consideration, a new grounds of rejection is made under 35 USC 103 over Robinson, Cordero-Coma, Andino, Kohn and Libin.
Applicant’s amendment renders the rejection under 35 USC 103 over Robinson, Cordero-Coma, Andino, Kohn and Chen moot. Specifically, the references do not teach the new limitation, “at least 80% by weight of spherical particles”. Thus, said rejection has been withdrawn. However, after further consideration, a new grounds of rejection is made under 35 USC 103 over Robinson, Cordero-Coma, Andino, Kohn, Libin and Chen.
Applicant’s amendment renders the rejection under 35 USC 103 over Robinson, Cordero-Coma, Andino, Kohn and Herweck moot. Specifically, the references do not teach the new limitation, “at least 80% by weight of spherical particles”. Thus, said rejection has been withdrawn. However, after further consideration, a new grounds of rejection is made under 35 USC 103 over Robinson, Cordero-Coma, Andino, Kohn, Libin and Herweck.
Applicant’s amendment renders the rejection under 35 USC 103 over Robinson, Cordero-Coma, Andino, Kohn and Peyman moot. Specifically, the references do not teach the new limitation, “at least 80% by weight of spherical particles”. Thus, said rejection has been withdrawn. However, after further consideration, a new grounds of rejection is made under 35 USC 103 over Robinson, Cordero-Coma, Andino, Kohn and Libin.
New Rejections
In light of Applicant’s amendments, the following rejections are newly added:
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 91, 92, 100, 102, 105-108, 111, 112, 122, 126-129, 130-133 and 137 are rejected under 35 U.S.C. 103 as being unpatentable over Robinson et al. (US 2008/0131484 A1, Jun. 5, 2008, hereafter as “Robinson”) in view of Cordero-Coma et al. (“Golimumab for Uveitis”, Ophthalmology, Volume 118, Issue 9, September 2011, Pages 1892.e3-1892.e4; hereafter as “Cordero-Coma”), Andino et al. (US 2015/0051581 A1, Feb. 19, 2015, hereafter as “Andino”), Kohn et al. (US 2017/0056504 A1, Sep. 2, 2015, hereafter as “Kohn”) and Libin et al. (US 2010/0173000 A1, Jul. 8, 2010, hereafter as “Libin”).
The claims are drawn to a composition for injection into a suprachoroidal space or supraciliary space, the composition comprising: at least 80% by weight of spherical particles, each spherical particle comprising a drug and a first polymer, wherein the drug is dispersed in the first polymer as an amorphous solid dispersion or as a plurality of drug crystals, and wherein the first polymer is biodegradable or bioerodible in the suprachoroidal space or supraciliary space after injection; and at least one excipient comprising a second polymer that acts as a binder to form the spherical particles into a flexible solid elongate body, wherein the second polymer is not incorporated into the spherical particles, and wherein the second polymer is water soluble and is dissolvable in physiological conditions of the suprachoroidal space or supraciliary space.
Regarding instant claims 91, 111, 112, 129 and 137, Robinson teaches intraocular biodegradable drug delivery systems (title; abstract). Robinson defines intraocular to include suprachoroidal ([0047]). In a particular embodiment, said drug delivery system comprises particles of a drug blended with a first polymer and extruded to form a filament or rod, the filament or rod is broken into pieces and further ground into particles with a size (diameter) between about 30-50 microns and then said particles are blended with additional quantities of drug and a second polymer ([0133]). The second mixture is then extruded into filaments or rods and sized to form the final implant ([0133]). Robinson notes that extrusion yields drug particles that are dispersed within a continuous polymer ([0127]-[0128]). It is noted that particles having only a diameter as a dimension implies that the particles are round/spherical in nature. Robinson further teaches that the first and second polymers can be different bioerodible/biodegradable polymers as well as the particular bioerodible/biodegradable polymers, polylactic-glycolic acid copolymer (PLGA) copolymers ([0020], [0041], [0057], [0132] and [0133]). Robinson also teaches incorporating hydrophilic end groups to enhance hydrolysis/degradation of PLGA including the particular water soluble polymer, polyethylene glycol ([0115]). In a particular embodiment, Robinson teaches the combination of a biodegradable polymer, poly(D,L-lactide-co-glycolide), and a water soluble polymer, PEG-3350 ([0187]). Robinson also teaches that the drug delivery system is injectable ([0071]).
It is noted that the instant claims are product claims and any intended use recitation such as “for injection into a suprachoroidal space or supraciliary space” or the like does not alone show patentable distinction. A recitation of intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. In other words, if the prior art structure is capable of performing the intended use, then it meets the claim.
It is further noted that the term “flexible” is not explicitly recited in the reference, however, the reference teaches the same polymeric materials, PLGA and PEG, as claimed/elected. It is understood that a composition and its properties are inseparable (MPEP 2112.01). Thus, a skilled artisan would expect the same material to possess the same properties including flexibility. As such, the reference implicitly reads on the term “flexible”.
In regards to the limitation, “wherein said the second polymer is a water soluble polymer that is dissolvable in physiological conditions of the suprachoroidal space or supraciliary space”, Robinson teaches that the release of the active agent can be achieved by erosion of the biodegradable polymer matrix and by diffusion of the particulate agent into an ocular fluid with subsequent dissolution of the polymer matrix and release of the active agent and that the release kinetics of the active agent can be modified by varying a number of factors including the polymer matrix utilized (e.g., [0118]-[0119]). Thus, Robinson describes that the drug particles are released/dispersed from the drug delivery system once the polymer matrix degrades or erodes. While Robinson does not explicitly teach that the polymer matrix acts as a binder, the teaching that as the polymer matrix degrades or erodes and the drug particles are released/dispersed implies that the polymer matrix (excipient) acts as a binder to keep the particles from releasing/dispersing until the said polymer matrix degrades/erodes once placed in the ocular location. Regarding the type of polymer/binder (i.e., second polymer) and that is not incorporated into the spherical particles, Robison teaches that the first polymer (particles) and the second polymer (matrix) can be different ([0057]) and also teaches that incorporating hydrophilic end groups enhances hydrolysis/degradation of PLGA such as including the particular water soluble polymer, polyethylene glycol ([0115]) and exemplifies the particular water soluble polyethylene glycol, PEG-3350 ([0187]). Further, Robinson teaches that a pore former can be included in the matrix and exemplifies methocel (a chemically modified cellulose polymer with high solubility) ([0058]). It is noted that the claim recites, “at least one excipient comprising a second polymer that acts as a binder to form the spherical particles into a flexible solid elongate body, and wherein the second polymer is a water soluble polymer” and, as such, a methocel pore former would meet the water soluble polymer limitation.
While Robinson does not teach a particular embodiment combining all of the elements, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include a water soluble polymer that is not incorporated into the spherical particles, with a reasonable expectation of success because Robinson teaches that the first and second polymers can be different, that incorporating hydrophilic end groups enhances hydrolysis/degradation of PLGA such as including the particular water soluble polymer, polyethylene glycol, and that a methocel (a chemically modified cellulose polymer with high solubility) pore former can be included in the matrix. A skilled artisan would have been motivated to incorporate hydrophilic end groups into only the matrix (second) polymer and/or incorporate a methocel (a chemically modified cellulose polymer with high solubility) pore former into only the matrix (second) polymer because Robinson teaches that such modifications enhance degradation and would allow the skilled artisan to modify the degradation of the matrix and thereby the release of the active agent to a desired release profile.
While Robinson teaches immunosuppressants as suitable drugs ([0106]), Robinson is silent to the particular immunosuppressant agent, golimumab (an anti-TNF alpha agent).
Cordero-Coma teaches subcutaneous administration of golimumab for the treatment of the particular ocular condition, uveitis (page 1892.e3 and Figure 2).
Andino, in the field of ophthalmic therapies, teaches administering a medicament via microneedle into ocular tissues (e.g., suprachoroidal space) for the treatment of the eye ([0002] and [0113]). Andino teaches that a wide range of ocular diseases and disorders may be treated including uveitis, glaucoma, diabetic macular edema or retinopathy, macular degeneration, retinoblastoma, and genetic diseases ([0343]). Andino further teaches the particular medicament, golimumab, as a suitable medicament ([0351]).
The references are all drawn to ophthalmic therapies, thus, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to include the particular immunosuppressant drug, golimumab, in the invention of Robinson as suggested by Cordero-Coma/Andino with a reasonable expectation of success. A skilled artisan would have been motivated to do so because Cordero-Coma generally teaches that golimumab is effective in the treatment of ocular conditions such as uveitis and Andino teaches that local delivery, including into the suprachoroidal space of the eye, of medicaments such as golimumab is suitable for the treatment of various ocular conditions.
While Robinson teaches homogenous distribution/dispersion of the active agent particles ([0066] and [0087]) and Cordero-Coma and Andino teach golimumab as a suitable active agent in the treatment of ocular conditions, the references are silent to the particular drug, golimumab, in the form of an amorphous solid dispersion or a plurality of drug crystals.
Kohn teaches that golimumab is known to be in crystalline form ([0067]).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to include golimumab in crystalline form in the invention of Robinson/Cordero-Coma/Andino as suggested by Kohn with a reasonable expectation of success. A skilled artisan would have been motivated to do so because Kohn teaches that golimumab is known to be available in crystalline form for pharmaceutical formulations. One of ordinary skill would have reasonably expected to utilize the active agent in the form it is available, which in this case, golimumab is known in the art to be available in crystalline form.
Robinson is silent to the percentage of particles in the biodegradable implant (e.g., at least 80%) (instant claim 91), wherein the at least one excipient consists of the second polymer (instant claim 129); and wherein the second polymer is polyvinylpyrrolidone or a polyvinylpyrrolidone co-vinyl acetate (instant claim 137).
Libin teaches a dispensing device, such as one in the form of a rod, having a polymer with is combined with a therapeutic agent in the form of a microparticle/microsphere/micro-capsule which is “hyper-compressed” to form a controlled release dispensing device for the local delivery (implantable or injectable) of therapeutic agents to the eye (abstract; [0023], [0051], [0071] and [0082]). Libin teaches that the term microsphere is used to describe a substantially homogenous structure that comprises a drug that is dispersed evenly in a polymeric matrix ([0071]). Libin also teaches that from 1-5 wt% of a binder, such as polyvinyl pyrrolidone, may be homogenously mixed with the microparticles prior to the compression step ([0074]). It is apparent from the Examples in Libin that the microparticles are the only required ingredient in the dispensing device. In light of the teaching that the binder is permitted in amounts of 1-5%, it is readily understood that the microparticles can be included in the dispensing device in amounts of 95-99% (i.e., greater than 80%).
Robinson and Libin are both drawn to injectable compositions comprising drug/polymer particles and a polymeric binding agent for treatment of the eye, thus, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include particles in an amount of at least 80% of the composition and polyvinyl pyrrolidone as the sole binder/excipient into Robinson as suggested by Libin with a reasonable expectation of success. A skilled artisan would have been motivated to do so because Libin teaches that it is suitable to include microparticles in an amount of 95-99% when a binder such as polyvinylpyrrolidone is present in a similar system to Robinson to allow for controlled release of an active agent over time to the eye.
Regarding instant claim 92, Robinson teaches that the particles comprise a polymer, particularly, biodegradable polymers including polylactic-glycolic acid copolymer ([0020], [0041] and [0133]).
Regarding instant claims 100, 102 and 126, Robinson teaches a particular embodiment comprising 10% of PEG3350 (a water-soluble polymer) ([0187]).
Regarding instant claims 105-107, said claims include limitations regarding buckling force or flexural rigidity. Robinson is silent to said limitations. However, said limitations are considered property limitations. It is noted that a chemical composition and its properties are inseparable (MPEP 2112.01). A skilled artisan would expect the same composition to possess the same properties (MPEP 2112.01).
Regarding instant claim 108, Robinson further teaches that the implant may be any size or shape compatible with the selected site of implantation ([0121]).
Regarding instant claim 122, Robinson teaches that the drug/polymer particles have diameters between about 30-50 microns and that said particles are blended with additional quantities of drug and a second polymer to form the implant ([0133]). Accordingly, Robinson teaches a mixture of diameters between about 30-50 microns.
Regarding instant claim 127, Robinson implicitly teaches spherical particles, as discussed above, and further teaches that the drug/polymer particles have diameters between about 30-50 microns ([0133]). Accordingly, Robinson teaches spherical particles in the micrometer range (i.e., microspheres).
Regarding instant claim 128, it is noted that said claim is deemed a product-by-process claims due to the limitation, “formed by spray drying, coacervation, or emulsification” and as such, determination of patentability is based on the product itself, not by the method in which it is made. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process (MPEP 2113). As discussed above, Robinson implicitly teaches spherical particles in the micrometer range (i.e., microspheres).
Regarding instant claim 130, said claim recites, “wherein the flexible solid elongate body has a reduced flexural frigidity when in contact with the suprachoroidal space or supraciliary space”. Robinson is silent to said limitation. However, said limitation is considered a property of the elongate body. It is noted that a chemical composition and its properties are inseparable (MPEP 2112.01). A skilled artisan would reasonably expect the same composition to possess the same properties (MPEP 2112.01).
Regarding instant claims 131-133, Robinson teaches release of a therapeutic effective amount of drug over a period of time between 10 days to one year or longer (abstract). In a particular embodiment, an amount of drug was released over about a 3 to 4 month period ([0183]). Said teaching implies 100% of the drug was released around the 3 to 4 month mark. 100% reads on “a minimum of 50%” and 3 to 4 months reads on “after 7 days”, “after 3 days” and “after 1 day”.
Thus, the combined teachings of Robinson, Cordero-Coma, Andino, Kohn and Libin render the instant claims prima facie obvious.
Claims 94 and 96-99 are rejected under 35 U.S.C. 103 as being unpatentable over Robinson et al. (US 2008/0131484 A1, Jun. 5, 2008, hereafter as “Robinson”) in view of Cordero-Coma et al. (“Golimumab for Uveitis”, Ophthalmology, Volume 118, Issue 9, September 2011, Pages 1892.e3-1892.e4; hereafter as “Cordero-Coma”), Andino et al. (US 2015/0051581 A1, Feb. 19, 2015, hereafter as “Andino”), Kohn et al. (US 2017/0056504 A1, Sep. 2, 2015, hereafter as “Kohn”) and Libin et al. (US 2010/0173000 A1, Jul. 8, 2010, hereafter as “Libin”), as applied to claim 91 above, and further in view of Chen et al. (US 2003/0077297 A1, Apr. 24, 2003, hereafter as “Chen”).
Robinson, Cordero-Coma, Andino, Kohn and Libin teach the elements discussed above.
Robinson, Cordero-Coma, Andino, Kohn and Libin are silent to a surface barrier coating and the particular surface barrier coating material, sterol.
Chen, in the field of pharmaceutical formulations, teaches that a surface coating of an interfacial modifying agent can be applied to active agent particles to modify the surface properties of said active agent, wherein the interfacial modifying agent is selected from a surfactant, a hydrophilic polymer, a lipid, a gelatin, a saccharide, or a mixture thereof ([0223]). Chen teaches that if faster dissolution is desirable, the surface coating may be one that speeds wetting and comprises, for example, a hydrophilic surfactant, a sugar such as lactose, sucrose, or dextrose, or a hydrophilic polymer and if controlled release is desirable, e.g., sustained and/or delayed release, a suitable sustained and/or delayed release coating can be applied, for example, cellulose derivatives, polysaccharides, acrylic polymers, lipophilic surfactants, triglycerides, and mixtures thereof ([0223]). Chen also teaches that sterols and derivatives of sterols are suitable surfactants that can be hydrophilic or lipophilic ([0148]-[0149]; Table 10). Chen further teaches immunosuppressants as suitable active agents ([0047]) as well as ocular formulations ([0312]).
The references are all drawn to pharmaceutical formulations comprising an immunosuppressant active agent suitable for treating the eye, thus, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to include a sterol as an active agent particle coating as suggested by Chen into the invention of Robinson/Cordero-Coma/Andino/Kohn/Libin with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to do so because Chen teaches that applying said coating allows one to modify the surface properties of the active agent and sterols, in particular, can be hydrophilic or lipophilic which allows a skilled practitioner to alter the release of the active agent depending on the desired properties (i.e., faster dissolution or controlled release).
Thus, the combined teachings of Robinson, Cordero-Coma, Andino, Kohn, Libin and Chen render the instant claims prima facie obvious.
Claims 109 and 110 are rejected under 35 U.S.C. 103 as being unpatentable over Robinson et al. (US 2008/0131484 A1, Jun. 5, 2008, hereafter as “Robinson”) in view of Cordero-Coma et al. (“Golimumab for Uveitis”, Ophthalmology, Volume 118, Issue 9, September 2011, Pages 1892.e3-1892.e4; hereafter as “Cordero-Coma”), Andino et al. (US 2015/0051581 A1, Feb. 19, 2015, hereafter as “Andino”), Kohn et al. (US 2017/0056504 A1, Sep. 2, 2015, hereafter as “Kohn”) and Libin et al. (US 2010/0173000 A1, Jul. 8, 2010, hereafter as “Libin”), as applied to claim 91 above, and further in view of Herweck et al. (US 2008/0207756 A1, Aug. 28, 2008, hereafter as “Herweck”).
Robinson, Cordero-Coma, Andino, Kohn and Libin teach the elements discussed above.
Robinson, Cordero-Coma, Andino, Kohn and Libin are silent to a lubricant, wherein the lubricant is a fatty acid, lipid, sterol or oil.
Herweck generally teaches lubricating tissues, implants, and surgical tools by coating said tissues, implants, and surgical tools with a bioabsorbable oil to prevent adhesion between various tissues ([0071]).
Robinson and Herweck are drawn to implantable devices, thus, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to include a lubricant such as a bioabsorbable oil as suggested by Herweck into the invention of Robinson/Cordero-Coma/Andino/Kohn/Libin with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to do so because Herweck teaches that coating an implantable device effectively reduces the occurrence of adhesion between tissues.
Thus, the combined teachings of Robinson, Cordero-Coma, Andino, Kohn, Libin and Herweck render the instant claims prima facie obvious.
Response to Arguments
The arguments filed 9/9/2025 regarding the 103 rejection over Robinson, Cordero-Coma, Andino and Kohn, the 103 rejection over Robinson, Cordero-Coma, Andino, Kohn and Chen, the 103 rejection over Robinson, Cordero-Coma, Andino, Kohn and Herweck, the 103 rejection over Robinson, Cordero-Coma, Andino, Kohn and Peyman are moot in view of the withdrawn rejections discussed above.
Conclusion
All claims have been rejected; no claims are allowed.
Correspondence
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/CASEY S HAGOPIAN/Examiner, Art Unit 1617