DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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.
Receipt and consideration of Applicant’s amended claim set and Applicant’s arguments/remarks submitted on March 18, 2026 are acknowledged.
All rejections/objections not explicitly maintained in the instant office action have been withdrawn per Applicant’s claim amendments and/or persuasive arguments. Applicant’s claim amendments have necessitated new grounds of rejections set forth below.
Status of the Claims
Claims 37, 39-55, and 57-61 are pending and under consideration in this action. Claims 1-36, 38, and 56 are cancelled. Claims 60 and 61 are newly added.
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.
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 37, 39-42, 44, 47-55, and 57-61 are rejected under 35 U.S.C. 103 as being unpatentable over Haffner et al. (Haffner) (US 2012/0078362 A1; of record).
With regards to Claims 37, 51, 57, 60, and 61, Haffner discloses drug delivery devices, which are used in methods for the treatment of ocular disorders requiring targeted and controlled administration of a drug to an interior portion of the eye for reduction or prevention of systems of the disorder.
Haffner’s method of treating an ocular condition or disorder in an intraocular target tissue comprises: making an incision in the temporal portion of the eye (reading on accessing an interior of an eye), advancing a delivery device associated with a drug delivery implant through the cornea of the eye and across the anterior chamber of the eye, inserting the drug delivery implant into the suprachoroidal space of the eye, wherein the drug delivery implant comprises, an elongate outer shell having a proximal end, a distal end, said outer shell being shaped to define an interior lumen (chamber); at least a first drug positioned within said interior lumen; positioning said implant such that at least one of said one or more regions of the drug release are located proximate an intraocular target; and withdrawing the delivery device from the eye, wherein drug elutes from the implant in sufficient quantity to treat an ocular condition or disorder (Haffner claim 16; para.0008, 0093, 0094).
The implant further comprises a retention protrusion (reading on anchor) for anchoring (e.g., affix, secure, or otherwise attach, either permanently or transiently, to a suitable target intraocular tissue) the implant to ocular tissue (para.0032, 0070, 0146, 0159). Among the suitable target intraocular tissue for the implants to be anchored into include the sclera (para.0032).
In some embodiments, the retention protrusion (anchor) additionally includes a shunt feature (reading on anchor comprising a stem having a lumen). The shunt can be configured to provide a fluid flow path for draining aqueous humor from the anterior chamber of an eye to an outflow pathway to reduce intraocular pressure. The shunt feature of the implant may be positioned in any physiological location that necessitates simultaneous drug delivery and transport of fluid from a first physiologic sit to a second site (para.0173).
At least one lumen (chamber) can extend through the shunt portion of the implant. In some embodiments, there is at least one lumen that operates to conduct the fluid through the shunt portion of the implant. In some embodiments, the lumen extends substantially through the longitudinal center of the shunt (para.0175). In an embodiment, a lumen of the device is configured to transport therapeutic agents between the inlet section and the outlet section (par.0188).
In several embodiments, the orifices are covered (wholly or partially) with one or more elution membranes that provide a barrier to the release of drug from the interior lumen of the implant shell. In several embodiments, the elution membrane is permeable to the therapeutic agent, to bodily fluids or to both. In other embodiments, the membrane is fully or partially coated with a biodegradable or bioerodible material, allowing for control of the inception of entry of bodily fluid, or egress of therapeutic agent from the implant (para.0134).
Haffner encompasses administering more than one drug, such as when more than one drug may be desired for treatment of a particular pathology or a second drug is administered such as to counteract a side effect of the first drug (para.0259).
In some embodiments, the implant is formed with one or more dividers positioned longitudinally within the outer shell, creating multiple additional sub-lumens within the interior lumen of the shell (para.0142). A drug is housed within the interior lumen of the implant. In some embodiments, one or more of the internal lumens may contain a different drug or concentration of drug, which may be delivered simultaneously (combination therapy) or separately (para.0156).
In some embodiments, at least one lumen extends through the shunt portion of the implant. In some embodiments, there is at least one lumen that operates to conduct the fluid through the shunt portion of the implant. In certain embodiments, each lumen extends from an inflow end to an outflow end along a lumen axis. In some embodiments, the lumen extends substantially through the longitudinal center of the shunt (para.0140). Additional outflow orifices may be positioned in more distal locations, up to or beyond the point where the interior lumen housing the drug or therapeutic agent begins (par.0141). In some embodiments, an impermeable partition is used to seal drug(s) within the lumen, such that the sole route of exit from the implant is through the region of drug release (para.0158).
The therapeutic agents utilized with the drug delivery implant may include one or more drugs, either alone or in combination (para.0259, 0311). Haffner also discloses that their systems also relate to delivery instruments for implanting an implant for delivering a drug to the eye (para.0201). The delivery instrument may be configured to deliver multiple implants. The implants may be arranged in tandem, or serially for implant numbers greater than two, within the device (para.0215). The placement and implantation of the implant may be performed using a gonioscope or other conventional imaging equipment (para.0227).
Following implantation at the desired site within the eye, drug is released from the implant in a targeted and controlled fashion, based on the design of the various aspects of the implant, preferably for an extended period of time (para.0090).
When the implant is advanced through the tissue and such that it is no longer in the lumen of the delivery instrument, the delivery instrument is retracted, leaving the implant in the eye tissue (para.0226).
With regards to Claim 39, among the examples of drugs that may be used include anti-vascular endothelial growth factor (anti-VEGF) drugs such as ranibizumab and bevacizumab (para.0311, 0313).
With regards to Claims 40 and 48, in embodiments, duration of drug release is desired over time. In some embodiments, an implant is capable of delivering a drug at a controlled rate to a target tissue for a period of several (i.e., at least three) months (para.0300).
With regards to Claims 42 and 59, in an embodiment, the drug diffuses through the shell and into the intraocular environment. The shell of the implant may be permeable, semipermeable, or impermeable to the drug (para.0095, 0109). The implant may also further include a coating control the release rate of the drug. For example, a coating may be added to either increase the effective thickness of the region of drug release or decrease the overall permeability of that portion of the implant, resulting in a reduction in drug elution (para.0274).
In some embodiments, there are provided coatings that are biodegradable. In some embodiments, two or more polymeric coatings are positioned on a surface of the outer shell. In some embodiments, the coatings are optionally placed on the outer surface of the shell, positioned between the drug and the interior surface of the outer shell, and/or positioned to envelop the drug within the interior lumen (para.0028). In several embodiments, biodegradation of the barriers or coatings is triggered by an externally originating stimulus, such as, for example, application of heat, ultrasound, and radio frequency, and the like (para.0029).
With regards to Claim 44, non-continuous or pulsatile release may also be desirable. This may be achieved, for example, by manufacturing an implant with multiple sub-lumens, each associated with one of more regions of drug release. In some embodiments, additional polymer coatings are used to prevent drug release from certain regions of drug release at a given time, while drug is eluted from other regions of drug release at that time. Other embodiments additionally employ one or more biodegradable partitions as described above to provide permanent or temporary physical barriers within an implant to further tune the amplitude or duration of period of lowered or non-release of drug from the implant. Additionally, by controlling the biodegradation rate of the partition, the length of a drug holiday may be controlled. In some embodiments, the biodegradation of the partition may be initiated or enhanced by an external stimulus. In some embodiments, the externally originating stimulus may be laser energy (para.0285).
Achieving local ocular administration of a drug can be accomplished using a drug eluting implant, a portion of which, could be positioned in close proximity to the target site of action within the eye or within the chamber of the eye where the target site is located (e.g., anterior chamber, posterior chamber, or both simultaneously). Use of a drug eluting implant could also allow the targeted delivery of a drug to a specific ocular tissue, e.g., the macula, the retina, the ciliary body, the optic nerve, or the vascular supply to certain regions of the eye. Use of a drug eluting implant could also provide the opportunity to administer a controlled amount of drug for a desired amount of time, depending on the pathology. For instance, some pathologies may require drugs to be released at a constant rate for just a few days, others may require drug release at a constant rate for up to several months, still others may need periodic or varied release rates over time, and even others may require periods of no release (e.g., a “drug holiday”) (para.0082).
In some embodiments, the implants are positioned such that the regions of the implant from which drug is released are located sufficiently near an intraocular target to allow substantially all of the drug released from the implant to reach the intraocular target (para.0047).
Haffner discloses that in some ocular disorders, therapy may require a defined kinetic profile of administration of drug to the eye. The ability to tailor the release rate of a drug from the implant can similarly be used to accomplish achieve a desired kinetic profile. For example, the composition of the outer shell and any coatings can be manipulated to provide a particular kinetic profile of release of the drug. Additionally, the design of the implant itself, including the thickness of the shell material, the thickness of the shell in the regions of drug release, the area of the regions of drug release, and the area and/or number of any orifices in the shell provide a means to create a particular drug profile (para.0281).
In certain embodiments, zero-order release of a drug may be achieved by manipulating any of the features and/or variables discussed above alone or in combination so that the characteristics of the implant are the principal factor controlling drug release from the implant (para.0282).
In other embodiments, pseudo zero-order release (or other desired release profile) may be achieved through the adjustment of the composition of the implant shell, the structure and dimension of the regions of drug release, the composition of any polymer coatings, and use of certain excipients or compounded formulations, the additive effect over time replicating true zero-order kinetics (para.0283).
Use of a drug eluting implant can provide the opportunity to administer a controlled amount of drug for a desired amount of time, depending on the pathology. For example, some pathologies may require drugs to be released at a constant rate for just a few days, other may require drug release at a constant rate for up to several months, still other may need periodic or varied release rates over time, and even others may require periods of no release (e.g., a drug holiday) (para.0082). The implant may also be designed so that the drug is ready for immediate release during or soon after implantation (para.0119).
The devices are capable of controlled release of one or more drugs (abstract). In an embodiment, the implant is configured to deliver one or more drugs to anterior region of the eye in a controlled fashion while in other embodiments the implant is configured to deliver one or more drugs to the posterior region of the eye in a controlled fashion. In other embodiments, the implant is configured to simultaneously deliver drugs to both the anterior and posterior region of the eye in a controlled fashion (para.0092).
With regards to deployment of the second and third ocular implant as recited in Claims 41, 51, 52, 53 and the drug in the second implant as recited in Claim 58, as discussed above, Haffner discloses a delivery instrument that may be configured to deliver multiple implants, which may be arranged in tandem or serial (para.0215). As discussed above, Haffner also discloses that for some ocular disorders, the therapy may require the use of more than one drug and may require a drug with a specifically defined kinetic profile of administration to the eye (e.g., zero-order release, pseudo zero-order release, or non-continuous or pulsatile release). In light of this disclosure, one of ordinary skill in the art would have found it prima facie obvious before the effective filing date of the instant invention to have a system with at least two implants as disclosed by Haffner, optimizing the number of implants deployed by the delivery instrument and the drug(s) contained in each implant based on art recognized factors such as condition being treated, duration of treatment, the amount of drug needed for treatment, the number of drugs needed for the treatment regimen, and/or timing and/or duration of each drug’s release. One of ordinary skill in the art would have been motivated to do so in order to obtain the advantage of being able to better customize and optimize the drug therapy for the ocular disorder to be treated. For example, the multiple implant system design would allow for the use of combination of drugs having different kinetic profile requirements, the use of a first drug with a second drug administered to counteract the side effect of the first drug, which is released only when needed, allow for targeted delivery of a drug in different locations of the eye (e.g., anterior and posterior chambers), and allow for a larger volume and longer treatment duration with the same drug. Furthermore, the multiple implant system design would also allow for only a patient to only have to undergo a single implantation procedure and minimize the number of incisions needed, thus offering additional benefits such as reducing chances of infections and other complications accompanying multiple incisions for implantation and multiple procedures. One of ordinary skill in the art would have had reasonable expectation of success in doing so as Haffner discloses that their disclosed delivery instrument may be configured to deliver multiple implants, indicating that a system having at least two of their disclosed implants is contemplated.
With regards to the time and duration of the drug elution as recited in Claims 40, 47, 48, and 51, as discussed above, Haffner discloses various design embodiments for controlling the timing and duration of drug release (e.g., coating, upon stimulus application, etc.), and discloses that the drug may be delivered for a period of at least three months, may be released immediately, and may have delayed release or that the release of the drug may be at a later time upon stimulus application. In light of these disclosures, one of ordinary skill in the art would have found it prima facie obvious and would have been motivated to engage in routine experimentation to determine the optimal timing and duration of the release of each drug from each implant based on art recognized and prior art disclosed factors, such as the eye condition to be treated, the combination of drugs being used, and the progression of the disease being treated. 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. In re Aller, 220 F. 2d 454, 105 USPQ 233 (CCPA 1955).
With regards to the pattern of positioning as recited in Claims 49, 50, 54, and 55, as discussed above, Haffner discloses that the delivery instrument may be configured in various arrangements, and discloses positioning the implant proximate to the intraocular target. In light of this disclosure, one of ordinary skill in the art would have found it prima facie obvious and would have been motivated to engage in routine experimentation to determine the optimal placement of each implant, which in turn will determine the spacing distance between the implants, based on art recognized and prior art disclosed factors, such as, where the implants should be delivered (e.g., posterior chamber, ciliary body), the condition being treated, and the area of the eye needing treatment and drug delivery. 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. In re Aller, 220 F. 2d 454, 105 USPQ 233 (CCPA 1955).
Therefore, the claimed invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention, because the teachings of the prior art reference is fairly suggestive of the claimed invention.
Claims 43, 45, and 46 are rejected under 35 U.S.C. 103 as being unpatentable over Haffner et al. (Haffner) (US 2012/0078362 A1; of record) as applied to claims 37, 39-42, 44, 47-55, and 57-61, further in view of Coppeta et al. (Coppeta) (US 2012/0035528 A1; of record).
The teachings of Haffner as they apply to Claims 37, 39-42, 44, 47-55, and 57-61are set forth above and incorporated herein.
Haffner does not appear to explicitly disclose: (i) wherein the membrane comprises one or more of the elements recited in Claim 43; (ii) or wherein the stimulus comprises a laser energy from a laser selected from those recited in Claims 45 and 46. Coppeta is relied upon for these disclosures. The teachings of Coppeta are set forth herein below.
Coppeta discloses implantable devices for laser-activated reservoirs used to deliver an active pharmaceutical ingredient (API) to the interior of the eye for the treatment of ocular conditions (par.0002, 0148). The devices and techniques allow for the selective release of an API using laser irradiation of a hermetically-sealed reservoir or reservoirs. Coppeta discloses that this is especially useful for devices that have been implanted in the transparent issues of the eye, in which the non-invasive and efficacious introduction of a laser beam may be easily accomplished. Coppeta disclose that because the devices are hermetically sealed, they are also highly impermeable to water, water vapor or reactive gases such as oxygen. Thus, these devices are capable of providing long-term viability for APIs that are sensitive to chemical change, such as, for example, degradation by moisture or oxygen (para.0010).
The devices use materials that are both capable of providing a low-permeability barrier and can be breached by laser irradiation (para.0011). The laser may be a dye laser or ND:YAG laser (para.0018).
Among the suitable API that may be used include anti-VEGF agents such as bevacizumab and ranibizumab (para.0019).
The drug delivery devices can be implanted into the eye with minimal intervention, are hermetically sealed to protect an API payload over time, and can be laser activated through the retina to selectively release the API as needed (para.0052, 0130).
The drug delivery device reservoirs can be hermetically sealed using a variety of techniques. In some embodiments, the drug delivery device includes a hermetic seal formed between and joining the structural elements that form the shell or low-permeability barrier (para.0126). In some embodiments, the hermetic sealing material may be a metal, such as gold (e.g., gold foil), platinum, titanium, stainless steel or combinations thereof (0071-0072, 0075, 0126).
Coppeta discloses that in general, laser activation can be facilitated by providing an area or target on the drug delivery device that is capable of being breached using a pulse or series of pulses of laser radiation. The metal surface may be treated to produce an absorbing surface. A laser absorbing activation site enables laser energy to be directed and the size and location of the opening to be controlled (para.0134). The laser irradiation may be a Nd:YAG laser (para.0018). The Nd:YAG nanosecond lasers used in ophthalmic secondary cataract laser surgery, for example, have been used to perforate representative thicknesses of gold foil which may be used to construct a reservoir segment (para.0135).
Coppeta’s implants and methods can achieve controlled release, sustained release, pulsatile release, and delayed release drug elution profiles (para.0144-0155).
Haffner discloses that following implantation at the desired site within the eye, drug is released from the implant in a targeted and controlled fashion, based on the design of the various aspects of the implant, such as the degree of permeability of the shell. Haffner further discloses that a coating may further be added to the implant to further control the release rate of the drug. Particularly in the case where a drug therapy requires at least one drug that is only released on an as-needed basis, requires a delayed release, or is sensitive to degradation from the environment during storage, one of ordinary skill in the art would have found it prima facie obvious before the effective filing date to combine the teachings of Haffner with the teachings of Coppeta, and apply a hermetic sealing material as disclosed by Coppeta, such as gold foil, around at least one of Haffner’s implants, in particular, one that holds a drug that is released only on an as-needed basis, requires a delayed release, or is sensitive to degradation from the environment during storage. One of ordinary skill in the art would have been motivated to do so as it would allow for the drug release from that implant to be more precise and optimized to release only when it is needed as its release would be initiated by an external stimulus, such as a dye laser or Nd:YAG laser, which is non-invasive and efficacious, when needed, and it would provide long-term viability of drugs that are sensitive to chemical change, such as, degradation by moisture or oxygen. It would also allow for a more customized and optimized ocular drug therapy system that includes an implant allowing sustained release of a drug beginning at the time of implantation, while also having an implant that allows for release of a second drug when needed, which is initiated at the time of need by an external stimulus (e.g., Coppeta’s dye laser or ND:YAG laser). One of ordinary skill in the art would have had a reasonable expectation of success in doing so because Haffner allows for a coating and laser energy to be applied to their implant, and Coppeta’s hermetic sealing material such as gold foil is suitable for use in ocular implants.
Therefore, the claimed invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention, because the combined teachings of the prior art references is fairly suggestive of the claimed invention.
Response to Arguments
Applicant's arguments filed March 18, 2026 have been fully considered. Applicant notes that in addition to newly added claims 60 and 61, independent claims 37 and 51 have been amended, e.g., with new limitations regarding the anchoring component.
The rejections set forth above have been modified to address the newly added and amended claims. In particular, the Haffner reference discussed above in detail is relied upon for the amended features.
Conclusion
Claims 37, 39-55, and 57-61 are rejected. No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MONICA A. SHIN whose telephone number is (571)272-7138. The examiner can normally be reached Monday-Friday (9:00AM-5:00PM EST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sue X Liu can be reached at 571-272-5539. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MONICA A SHIN/Primary Examiner, Art Unit 1616
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