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 .
Formal Matters
Receipt of Applicant’s response, dated 01/22/2026, is acknowledged.
Claims 1-18 and 20-21 are pending.
Claim 19 is canceled.
Claims 1, 3-5, and 8-14 are amended.
Claims 15-18 and 20-21 remain withdrawn from consideration as being drawn to a nonelected invention.
Claims 1-14 are under consideration in the instant Office action to the extent of the elected species, i.e., the at least one pharmaceutically active molecule is nerve growth factor.
OBJECTIONS/REJECTIONS WITHDRAWN
Drawings
The objection to Figure 3 set forth in the Office action dated 10/23/2025 is hereby withdrawn in light of Applicant’s amendments to Figure 3.
Specification
The objections to the abstract and to the specification set forth in the Office action dated 10/23/2025 are hereby withdrawn in light of Applicant’s amendments to the abstract and to the specification.
Claim Objections
The objections to claims 1, 5, and 9 set forth in the Office action dated 10/23/2025 are hereby withdrawn in light of Applicant’s amendments to the claims.
Claim Rejections - 35 USC § 112
The indefiniteness rejections of claims 1-14 set forth in the Office action dated 10/23/2025 are hereby withdrawn in light of Applicant’s amendments to the claims.
MAINTAINED REJECTION
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 1-14 are rejected under 35 U.S.C. 103 as being unpatentable over Peyman (US 2019/0307551 A1, published 10/10/2019, filed on 06/25/2019, cited in IDS dated 03/24/2023) in view of Simpson et al (US 2004/0037813 A1, published 02/26/2004, cited in Notice of References Cited dated 10/23/2025) and Giudetti et al (IEEE, (2014), 1993-1995, published 11/06/2014, cited in Notice of References Cited dated 10/23/2025).
Peyman et al teach a corneal stroma graft implant to be inserted under a flap in a cornea of an eye so as to overlie the stromal tissue of the cornea and serve as a drug delivery implant (See entire document, e.g., [0019], [0284]). It can be implanted inside the corneal stroma where scarred stromal tissue or a stromal lenticule has been removed, such as in the SMILE procedure, in order to fill the cavity with an implant having a smooth surface and appropriate refraction matching the needed refraction of the eye (e.g., [0516]).
The implant may be formed from donor corneal tissue, a tissue culture grown cornea, or a 3-D printed cornea (e.g., [0020], [0551], [0578]). The implant may be formed from donor corneal stroma tissue by cutting one or more circular implant disks from donor corneal stromal tissue using a trephine or a femtosecond laser (i.e., refractive eye surgery), wherein the one or more circular implant disks have a diameter between approximately 3 millimeters and approximately 9 millimeters, and the one or more circular implant disks having a thickness between approximately 50 microns and approximately 100 microns (e.g., [0028], [0501], [0551], [0570]). After implantation, the implant and the stromal tissue of the cornea surrounding the implant are irradiated, and are thereby cross-linked, preventing an immune response to the implant and/or rejection of the implant by the patient (e.g., [0019]). The implant may be de-cellularized with a solution of 0.1-0.5% sodium dodecyl sulfate for simultaneous preservation of the implant and killing of any bacteria, viruses, or parasites of the implant prior to implantation (e.g., [0044]).
The implant can contain medication(s), including nerve growth factors, in forms including nanoparticles or microparticles, wherein the implant and the microparticles may contain polymers including polylactic-co-glycolic acid (PLGA) and polyethylene glycol (PEG) (e.g., [0291], [0312], [0315], [0362], [0391]).
Peyman et al do not teach specific motivation for using nerve growth factors as the medication or PLGA as the polymer in the microparticles, nor do they teach the amounts of medication or polymer in the microparticles to be used.
These deficiencies are made up for in the teaching of Simpson et al and Giudetti et al.
Simpson et al teach engineered tissue for implants including for drug delivery from electroprocessed collagen (See entire document, e.g., Abstract). The electroprocessed collagen compositions, which can comprise biologically compatible materials including poly(lactide-co-glycolides) (PLGA), one or more substances including nerve growth factors, and can be in forms including microparticles and nanoparticles, can be used to deliver the one or more substances to a desired location, such as in tissue scaffolding to deliver substances that will aid in the function of the scaffolding, such as delivery of nerve growth factor to promote innervation of an implanted scaffold (e.g., [0008], [0009], [0099], [0116], [0252], [0269]).
Giudetti et al teach synthesis of microparticles made of poly-lactic-co-glycolic acid (PLGA) and nerve growth factor (NGF) for nerve regeneration applications (See entire document, e.g., Abstract, Page 1993 Col. 2 Par. 2). PLGA was chosen as the microparticle material as it is a biocompatible and biodegradable co-polymer widely used for controlled release studies (e.g., Page 1993 Col. 2 Par. 3). The synthesis involves dissolving 30-35 mg PLGA in DCM, and separately preparing an emulsion from 200 microliters of aqueous solution comprising the molecule of interest, i.e., NGF, at a concentration of 10 micrograms per milliliter (this corresponds to ~57-~67 nanograms of NGF per microgram of PLGA microparticles; e.g., Page 1993 Col. 2 Par. 3). The loaded microparticles have a mean size of 6 to 8 microns and range between 1- and 20-microns diameter (e.g., Page 1994 Col. 1 Par. 4).
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 provide a drug delivering, cross-linked, de-cellularized corneal stroma graft implant to replace the recipient’s scarred corneal stroma tissue/lenticule, wherein the implant is formed from donor corneal stroma tissue obtained by cutting one or more circular implant disks from donor corneal stroma tissue using a femtosecond laser, the one or more circular implant disks having a thickness between approximately 50 microns and approximately 100 microns, wherein the implant contains PLGA, PEG, and microparticles made of PLGA loaded with medication being NGF having a concentration of ~57-~67 nanograms of NGF per microgram of PLGA microparticles and having a mean size of 6 to 8 microns and range between 1- and 20-microns diameter. One of ordinary skill in the art would have been motivated to do so in order to provide a corneal stroma graft implant that has the ability to promote innervation of said implant after implantation as is taught by Simpson et al. There would have been a reasonable expectation of success in using the microparticles of Giudetti et al in the implant of Peyman et al because the implant of Peyman et al is compatible with microparticles comprising NGF and PLGA.
The modified drug delivery implant of Peyman et al in view of Simpson et al and Giudetti et al renders obvious the drug delivery system of instant claims 1-14.
Regarding the ranges required by the instant claims, a prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art (In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003)). The modified drug delivery implant of Peyman et al in view of Simpson et al and Giudetti et al containing microparticles made of PLGA renders obvious the required ranges of PLGA recited in instant claims 1 and 3.
Response to Applicant’s Arguments
Applicant’s arguments filed on 01/22/2026 have been considered.
Applicant argues that with respect to Simpson, PLGA is an optional, additional material that is electroprocessed with collagen among other synthetic matrix materials, and therefore, even if PLGA is used in the compositions disclosed in this reference, it must be used in combination with collagen, the PLGA and collagen furthermore being electroprocessed, whereas in contrast, the matrix of the present invention does not necessarily comprise collagen and it is not at all an electroprocessed material as meant in Simpson. Applicant argues that while NGF is mentioned by Simpson as a possible therapeutic molecule to be administered by the matrices disclosed, it is shown that NGF is released only by electrospun collagen or gelatin matrices and no disclosure of NGF released by PLGA matrices is taught or suggested. Applicant argues that with respect to Giudetti, the reference discloses a method of NGF encapsulation by PLGA microspheres for use in nerve guide conduits to repair transected nerves, supported experimentally by use on in vitro cultures of dorsal root ganglia, and no disclosure is provided regarding the suitability of such microspheres in any corneal context, much less in a decellularized corneal stroma scaffold. Applicant argues that the combined references do not provide motivation to produce the present invention and, in particular, Simpson is limited to teachings on compositions including electroprocessed collagen and nothing about the release of NGF from an electroprocessed collagen matrix provides any information about the release of NGF from a matrix including at least 70% w/w PLGA. Applicant argues that similarly, Giudetti is limited to teachings on the use of PLGA microspheres in the context of nerve guide conduits for use with dorsal root ganglia and nothing about the release of NGF from a nerve guide conduit provides any information about the release of NGF from a corneal stroma scaffold or suggests that NGF should be encapsulated in microspheres for use in a corneal stroma scaffold. Applicant argues that since neither Simpson nor Giudetti provide any information on the use NGF in a corneal stroma scaffold as presently claimed, the references cannot provide any motivation to modify Peyman as alleged.
The above arguments regarding the matrix of the present invention not necessarily comprising collagen (or gelatin) and not being electroprocessed or electrospun has been fully considered by the Examiner but are not found persuasive because although the drug delivery system of the instant claims does not recite collagen or gelatin or being electroprocessed or electrospun, the drug delivery system of the instant claims is inclusive or open-ended due to the ‘comprising’ language and therefore does not exclude the presence of additional, unrecited elements. See MPEP 2111.03. The above arguments that Simpson does not teach or suggest NGF released by PLGA matrices, Giudetti does not disclose the suitability of the PLGA microspheres for use in nerve guide conduits to repair transected nerves in any corneal context, the combined references of Simpson and Giudetti do not provide motivation to produce the present invention, and neither Simpson nor Giudetti provide any information on the use NGF in a corneal stroma scaffold as presently claimed have been fully considered by the Examiner but are not found persuasive because the maintained rejection under 35 USC 103 is based on the combined teachings of Peyman, Simpson, and Giudetti and not their individual teachings nor the combination of solely the teachings of Simpson and Giudetti. Applicant is reminded that the test for combining references is what the combination of disclosures taken as a whole would suggest to one of ordinary skill in the art . In re McLaughlin, 170 USPQ 209 (CCPA 1971). References are evaluated by what they suggest to one versed in the art, rather than by their specific disclosures. In re Bozek, 163 USPQ 545 (CCPA 1969). Further, Applicant is reminded that the reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006). Applicant is reminded that one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). As is discussed in the maintained rejection under 35 USC 103 above, it would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, based on the teachings of Peyman, Simpson, and Giudetti, to provide a drug delivering, cross-linked, de-cellularized corneal stroma graft implant to replace the recipient’s scarred corneal stroma tissue/lenticule, wherein the implant is formed from donor corneal stroma tissue obtained by cutting one or more circular implant disks from donor corneal stroma tissue using a femtosecond laser, the one or more circular implant disks having a thickness between approximately 50 microns and approximately 100 microns, wherein the implant contains PLGA, PEG, and microparticles made of PLGA loaded with medication being NGF having a concentration of ~57-~67 nanograms of NGF per microgram of PLGA microparticles and having a mean size of 6 to 8 microns and range between 1- and 20-microns diameter in order to provide a corneal stroma graft implant that has the ability to promote innervation of said implant after implantation. Further, the implant of Peyman et al is taught as compatible with microparticles comprising NGF and PLGA which would provide a reasonable expectation of success in looking to the teachings of Simpson and Giudetti to modify the drug delivery implant of Peyman. Applicant is reminded that the art needs to provide a motivation and not the same motivation as Applicant or necessarily recognize the same problem/solution as Applicant. "In determining whether the subject matter of a patent claim is obvious, neither the particular motivation nor the avowed purpose of the patentee controls." KSR Int'l Co. v. Teleflex lnc., 550 U.S. 398,419 (2007). Instead, "any need or problem known in the field of endeavor at the time of invention and addressed by the patent can provide a reason for combining the elements in the manner claimed." Id. at 420.
Conclusion
No claims are allowable.
THIS ACTION IS MADE FINAL. 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 KAELEIGH ELIZABETH OLSEN whose telephone number is (703)756-1962. The examiner can normally be reached M-F 8-5 PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, David Blanchard can be reached at (571)272-0827. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/K.E.O./Examiner, Art Unit 1619
/DAVID J BLANCHARD/Supervisory Patent Examiner, Art Unit 1619