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 .
Status of the Claims
Claims 1, 2, 7, 9, 13, 15, 20, 24, 39 and 41-48 are currently pending in a response of 12/30/2025.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/30/2025 was filed before the mailing date of the instant action on the merits. The submission thereof is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner, and signed and initialed copy is enclosed herewith.
Withdrawn rejections:
Applicant's amendments and arguments filed 12/30/2025 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Any rejection and/or objection not specifically addressed below are herein withdrawn.
The following rejections are either reiterated or newly applied. They constitute the complete set of rejection and/or objection presently being applied to the instant application.
New Grounds of Rejections --- as necessitated by amendment
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 2, 7, 9, 13, 15, 20, 24, 39 and 41-48 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Each of claims 1, 13, 24, 39, 43 and 47 recites “about 50% GelMA”. However, the term “about” does not appear to be supported by the instant specification. Please note that “about” generally embraces ±10 % above and below the value. However, the specification does not support “51-55%” which is above value.
Each of claims 1, 13, 24 and 39 recites “about 10% to about 50% (w/v) PEGDA”, and each of claims 44 and 48 recites “about 50%”. The instant specification discloses “PEGDA is present between 1% and 40% or 40% or 50%” (see [0037] of the instant specification). However, there is no support of “41-49%”. Further as to about 50%, the term “about” does not appear to be supported by the instant specification. Please note that “about” generally embraces ±10 % above and below the value. However, the specification does not support “51-55%” which is above value.
Further, each of claims 1 and 13 recites “the composition exhibits an adhesion strength of about 20 kPa to about 90kPa”. However, the instant specification discloses “the cross-linked acryloyl-substituted gelatin has an adhesion strength of 20-90 kPa” ([0067], [0077]-30 of the specification), not the adhesion strength of the composition.
Each of claims 41, 42, 45 and 46 recites “the composition exhibits a burst pressure of at least about 20kPa (claims 41 and 45) and about 30kPa to about 35kPa (claims 42 and 46)”. The specification discloses “the cross-linked acryloyl-substituted gelatin has burst pressure of >20 kPa or between 30-35kPa” (see [0067] of the instant specification), not the composition exhibits such burst pressure.
Accordingly, it appears that those claims raise a new matter issue.
The remaining claims are also rejected due to the rejection of base claims 1 and 13.
If applicant disagrees, please indicate the location of the specification/figures and provide a proper explanation.
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 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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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, 2, 9, 13, 15, 22, 24, 39 and 41-48 remain/are rejected under 35 U.S.C. 103 as being unpatentable over Niu et al. (US2014/0377326A1, IDS of 07/07/2022) in view of Behnke et al. (US2018/0344738A1); Jones et al. (EP362188B1, of record); and further in view of Dana et al. (WO2017/139318A1, IDS of 07/07/2022).
Applicant claims the below claims 1, 13, 24 and 39 filed 12/30/2025:
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Level of Ordinary Skill in the Art
(MPEP 2141.03)
MPEP 2141.03 (I) states: “The “hypothetical ‘person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988). The level of skill is that of a medical/pharmaceutical tissue engineering research scientist, as is the case here, then one can assume comfortably that such an educated artisan will draw conventional ideas from medicine, pharmacy, physiology and chemistry— without being told to do so.
In addition, the prior art itself reflects an appropriate level (MPEP 2141.03(II)).
Determination of the scope and content of the prior art (MPEP 2141.01);
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02); and Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
Niu teaches a corneal endothelial composition comprising a transparent hydrogel scaffold and a single layer of cultured corneal endothelial cells on the surface of the scaffold and the hydrogel scaffold is comprised of at least one biopolymer, preferably gelatin, at least one synthetic polymer, and at least one photo-activated crosslinking agent (=photoinitiator), wherein the at least one synthetic polymer includes polyethylene glycol diacrylate (e.g., [0030], [0075] and claim 3 of prior art) which reads on the claimed diacrylated polyethylene glycol (PEGDA), the at least one biopolymer includes modified gelatin including gelatin methacrylate (GelMA) ([0013], [0023] and claims 7 and 17 of prior art) which reads on the claimed methacryloyl-substituted gelatin, and the at least one photo-activated crosslinking agent (=photoinitiator) includes eosin Y, 1-vinyl-2-pyrrolidone, and triethanolamine ([0083]) which reads on the claimed the subject matter of claim 9; the composition further comprises a therapeutic agent such as corticosteroid ([0079]); and this prior art teaches a method of treating crest-derived endothelial cells (CEC) caused by e.g., eye injuries (entire document including [0002] and the Examples) comprising applying hydrogel of gelatin-PEGDA to the eye injuries in the visible light spectrum (e.g., [0031] and [0128]) and the hydrogel scaffold is provided in the form of preferably sheet and thus it can be applied to the application site which suggest topical application ([0118]); and although Niu does not expressly teach the composition comprises a corneal cell within the composition as claimed, it would not make the invention distinct because even when the cell on the surface of the composition, it would promote tissue formation thereon and thus the claimed cell within the composition would be an obvious variation, in the absence of evidence to the contrary showing that when the cell is within the composition, tissue formation would highly enhanced compared to the cell on the surface of the composition(instant claims 1, 13, 24 and 39 (in part) and claim 9); and the composition may contain a carrier to maintain good viability of the corneal endothelial cells before transplantation ([0109]) (instant claims 2 and 15 ).
However, Niu does not expressly teach the amounts of GelMA and PEGDA of instant claims 1, 13, 24, 39, 43, 44, 47 and 48. The deficiencies are cured by Behnke.
Behnke discloses a pharmaceutical composition or cell preparation for ocular delivery contains LATS inhibitor, eye corneal endothelial cells (e.g., [0048], [0050] and [0053]), a photoinitiator (e.g., [2247-2248]), a localizing agent e.g., GelMA, PEGDA or its combination (e.g., [0054] and [2244]) and GelMA is used in an amount of about 10 to about 200mg/ml (=1 to 20%) ([2251]) which is within/overlaps the instant ranges of about 1 to about 50% or about 10% or about 20% or about 50% of GelMA. MPEP2144.05 I. OVERLAP OF RANGES In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). The localizing agent is able to carry corneal endothelial cells (CEC) and is suitable for use in the eye, and where CECs are delivered, preferably the localizing agent can facilitate CEC attachment to the cornea after surgical delivery to the surface of the eye ([2241]). Although Behnke does not expressly teach the amount of PEGDA, Behnke teaches localizing agent of GelMA, PEGDA or combination thereof ([2244]) and therefore, the amount of PEGDA would be optimized or adjusted depending on the intended purpose, type of formulation, relationship with other ingredients, etc. For example, GelMA is used in an amount of about 1 to about 20% ([2251]) and then, PEGDA would also be used in the same amount or lesser to act as the localizing agent. In this regard, please see MPEP 2144.05 (II)(A) stating: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here 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, 456, 105 USPQ 233, 235 (CCPA 1955). Further, it would have been obvious to modify the teachings of Niu with a combination of GelMA and PEGDA and amounts of Behnke because as taught by Behnke the localizing agent(s) carry CEC and facilitate CEC attachment to the cornea after surgical delivery to the surface of the eye as taught by Behnke (instant claims 1, 13, 24, 39, 43, 44, 47 and 48 – amounts of GelMA and PEGDA).
However, Niu in view of Behnke does not expressly teach molecular weight of PEGDA of instant claims 1, 13, 24 and 39. The deficiencies are cured by Jones.
Jones teaches a microparticle ocular implant composition comprising a polyalkylene glycol diacrylate (PEGDA) having molecular weight (Mw) of about 200 to 50,000 daltons (=0.2 to 50kDa) or 100 to 20,000 daltons (=0.1 to 20 kDa) which overlaps the claimed range of about 15kDa to about 40kDa. See MPEP2144.05 above (instant claims 1, 13, 24 and 39 – Mw of PEGDA), a photoinitiator, a biodegradable polymer, a therapeutic agent, and a gelatin ([0059], [0076] and claim 1 of prior art), and higher Mw of PEGDA results in an increase in drug release rate, and lower Mw of PEGDA has higher crosslinking density and therefore slower drug release rates ([0076]).
It would have been obvious to further define or select PEGDA of Niu or Niu in view of Behnke with certain lower Mw of Jones in order to provide enhanced properties including e.g., higher crosslinking density, as taught by Jones.
Further, the applied art alone or in combination does not expressly teach adhesion strength of instant claims 1, 13, 24 and 39 and burst pressure of instant claims 41, 42, 45, and 46, However, Niu teaches at [0114] that “[W]ith the preparation of the Niu, viable adhesion of the corneal endothelial layer occurs in living organisms even when the substrate is detached, and the viably adhered cells can grow in the body, and therefore, the substrate does not need to be maintained at a transplantation site for a long time, and the substrate that fell off in the anterior chamber can be removed within a given period after confirmation of the detachment. Even after early removal of the substrate, the corneal maintains transparency, and the recipient is basically expected to lead a normal life by around 2 weeks post-transplantation”. That is, Niu does not expressly teach numerical vale for adhesion strength, the observed functional retention indicates that such functional adhesion of the corneal endothelial layer, which supports adhesion without detachment under physiological conditions, which inherently adhesion strength sufficient to maintain tissue integrity.
In the alternative, Dana teaches compositions and methods of repair and reconstruction of defects and injuries to the cornea (abstract); the compositions comprises methacryloyl-substituted gelatin (GelMA), a visible light activated photoinitiator, and a pharmaceutically acceptable carrier (claim 1 of prior art);the Gel-CORE has a burst pressure higher than 15kPa ([0022]) that overlaps the ranges of at least about 20kPa or about 30 to about 35kPa of instant claims 41, 42, 45 and 46, and an adhesion strength higher than 40kPa ([0120]) that overlaps the instant range of about 20kDa to about 35kDa. See MPEP 2144.05 above (instant claims 1, 13, 24, and 39: adhesion strength and burst pressure); the methacryloyl-substituted gelatin has a degree of methacryloyl substitution between 30% and 85% (claim 2 of prior art) which overlaps the claimed range of between about 50% and about 90% (instant claims 7 and 20). See MPEP 2144.05 above; and the methacryloyl-substituted gelatin is present at a concentration between 5% and 25% (w/v) (claim 4 of prior art); the visible light activated photoinitiator includes Eosin Y, triethanol amine, vinyl caprolactam … combination thereof (claims 7-8 of prior art); the composition further comprises corneal cell or therapeutic agent (claims 11-12 of prior art); and this prior art further teaches a method for corneal reconstruction, comprising the steps of: a. applying a composition comprising a methacryloyl-substituted gelatin (GelMA), a visible light activated photoinitiator, and a pharmaceutically acceptable carrier to a corneal defect; and b. exposing the composition to visible light (claim 21 of prior art).
It would have been obvious to further define the methacryloyl-substituted gelation of Niu/Behnke with methacryloyl substitution degree of Dana in order to provide suitable repair and/or reconstruction treatment by applying the hydrogel.
It would have been obvious to further define the composition of Niu/Behnke with mechanical properties of adhesion strength and burst pressure of Dana in order to reconstruct the composition for healthy cornea, as taught by Dana.
In light of the foregoing, instant claims 1, 2, 7, 9, 13, 15, 20, 24, 39 and 41-48 are obvious over Niu in view of Behnke/Jones/Dana.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the combined references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant’s arguments have been fully considered, but are not persuasive for the reasons in the body of Action. In particular, Behnke discloses overlapping amounts (e.g., about 1 to about 20%) of GelMA (see e.g., [2251]); for the amount of PEGDA, please see MPEP 2144.05 (II)(A) stating: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here 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, 456, 105 USPQ 233, 235 (CCPA 1955), and applicant did not show criticality of the claimed range and thus such amount would be optimized; for the claimed properties of an adhesion strength, please see Niu ([0114]) and Dana; and lastly, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. In reKeller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In reMerck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). MPEP2145.
In light of the foregoing, applicant’s arguments are not persuasive.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the claims at issue are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 2, 7, 9, 13, 15, 20, 24, 39 and 41-48 remains/are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 37-42 and 46-57 of copending application No. 18/471748 in view of Niu/Behnke/Dana.
Although the claims at issue are not identical, they are not patentably distinct from each other because both claims require methacryloyl-substituted gelatin (GelMA), and visible light activated photoinitiator, overlapping amounts and substitution degree of the gelatin. However, copending ‘748 does not expressly teach diacrylated polyethylene glycol (PEGDA) and the amounts of GelMA and PEGDA, and adhesion strength. The deficiencies are cured by Niu/Behnke/Dana. Niu and Behnke disclose a combination of GelMA and PEGDA, and their amounts as noted above, and addition of PEGDA to the composition containing GelMA of copending ‘748 improves the cell attachment and therefore it would have been obvious to further add PEGDA to the composition of copending ‘748. Further, Behnke discloses overlapping amount of GelMA and amount of PEGDA would be optimized depending on the intended purpose, type of formulation, relationship with other ingredients such as GelMA, eye injury condition, relationship with other ingredient such as GelMA, minimum of side effects, etc. in the absence of criticality of the claimed range. Niu ([0114])/Dana ([0120]) disclose overlapping range of adhesion strength, and Dana ([0022] and the Examples) discloses overlapping burst pressure as noted above. It would have been obvious to modify patent ‘800 with adhesion strength and burst pressure in order to enhance the properties of the composition.
Consequently, the ordinary artisan would have recognized the obvious variation of the instantly claimed subject matter over the copending ‘748 subject matter in view of Niu/Behnke/Dana.
This is a provisional double patenting rejection since the conflicting claims have not yet been patented.
Claims 1, 2, 7, 9, 13, 15, 20, 24, 39 and 41-48 remains/are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of US patent no. 11,058,800B2 in view of Niu and Behnke.
Although the claims at issue are not identical, they are not patentably distinct from each other because both claims require methacryloyl-substituted gelatin (GelMA), and visible light activated photoinitiator, overlapping amounts and substitution degree of the said gelatin as noted above. However, patent ‘800 does not expressly teach PEGDA, and the amounts of GelMA and PEGDA. The deficiency is cured by Niu and Behnke. Niu and Behnke disclose GelMA and PEGDA and their amounts as noted above, and addition of PEGDA improves the cell attachment and therefore it would have been obvious to further add PEGDA to the composition of patent ‘880 containing GelMA. Further, Behnke discloses inside amount 10% of GelMA and 5% of PEGDA which is outside scope of the claimed range, and however, the claimed amount of PEGDA would be optimized depending on the intended purpose, injury condition, relationship with other ingredient such as GelMA, minimum of side effects, etc., in the absence of criticality of the claimed range. Niu ([0114])/Dana ([0120]) disclose overlapping range of adhesion strength, and Dana ([0022] and the Examples) discloses overlapping burst pressure as noted above. It would have been obvious to modify patent ‘800 with adhesion strength and burst pressure in order to enhance the properties of the composition.
Consequently, the ordinary artisan would have recognized the obvious variation of the instantly claimed subject matter over the patent ‘800 subject matter in view of Niu and Behnke.
Response to Arguments
Applicant’s arguments have been fully considered, but are not persuasive because Niu/Behnke/Dana can cure the deficiencies of copending ‘748 and patent ‘800 as noted above.
Conclusion
All examined claims are rejected.
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 KYUNG S CHANG whose telephone number is (571)270-1392. The examiner can normally be reached M-F 8-5.
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/KYUNG S CHANG/Primary Examiner, Art Unit 1613