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 03/27/2026 is acknowledged.
Claims 1-5, 8, and 10-18 are pending.
Claims 6-7 and 9 are canceled.
Claims 1, 5, and 15-18 are amended.
Claims 10-14 remain withdrawn from consideration as being drawn to a nonelected invention.
Claims 1-5, 8, and 15-18 are under consideration in the instant Office action.
OBJECTIONS/REJECTIONS WITHDRAWN
Claim Objections
The objections to claims 1 and 15-18 set forth in the Office action dated 12/29/2025 are hereby withdrawn in light of Applicant’s amendments to the claims.
Claim Rejections - 35 USC § 112(b)
The indefiniteness rejections set forth in the Office action dated 12/29/2025 are hereby withdrawn in light of Applicant’s amendments to the claims.
Claim Rejections - 35 USC § 103
The obviousness rejections of claims 1-3, 5, 7-8, and 15-18 over Yang et al in view of Hu et al and Liu et al and of claim 4 over Yang et al in view of Hu et al and Liu et al and further in view of Rafat et al set forth in the Office action dated 12/29/2025 are hereby withdrawn in light of Applicant’s amendments to the claims and in favor of the new grounds of rejection set forth below as necessitated by Applicant’s amendments to the claims.
NEW GROUNDS OF 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 1-3, 5, 8, and 15-18 are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al (CN 111201040 A, published 05/26/2020, cited in Notice of References Cited dated 12/29/2025) in view of Hu et al (CN 102304193 A, published 01/04/2012, cited in Notice of References Cited 02/27/2025), Liu et al (Int. J. Pharm., (2019), 565, 133-142, published 06/30/2019, cited in Notice of References Cited dated 12/29/2025), and Hayami (JP 2010037217 A, published 02/18/2010).
Yang et al teach a microparticle composition, wherein the microparticles comprise one or more biodegradable polymers or copolymers (See entire document, e.g., Abstract, “Biodegradable Polymers” on Page 83 of English translation). Yang et al teach use of the microparticle composition further comprising an effective amount of a pharmaceutically active compound to treat an ocular or other disorder that may benefit from topical or local delivery to the eye, wherein the disorder may be of the cornea, conjunctiva, aqueous humor, iris, ciliary body, phacoscleral, choroid, retinal pigment epithelium, neuroretina, optic nerve, or vitreous humor (e.g., Bottom of Page 81 of English translation).
The one or more biodegradable polymers or copolymers may be PLA, PLA-PEG copolymer, PVA, or combinations thereof (e.g., “Biodegradable Polymers” on Page 83 of English translation). By PLA is meant polylactic acid including any variant, such as, but not limited to, PLLA (poly-L-lactic acid), racemic PLLA (poly-L-lactic acid), PDLA (poly-D-lactic acid), and PDLLA (poly-DL-lactic acid), or mixtures thereof (e.g., “Biodegradable polymer-containing microparticles” on Bottom of Page 85 of English translation). The microparticles may comprise a hydrophobic polymer covalently bound to a hydrophilic biodegradable polymer including PLA-PEG copolymer (e.g., “Biodegradable polymer-containing microparticles” on Top of Page 86 of English translation).
PLA may comprise at least about 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% of the microparticle (e.g., “Biodegradable polymer-containing microparticles” on Top of Page 86 of English translation). The PLA may have a molecular weight of about 30 to 60 kD (e.g., “Biodegradable polymer-containing microparticles” on Top of Page 86 of English translation).
Hydrophobic polymers covalently attached to hydrophilic polymers may be present in an amount of from about 0.5% to about 10% of the microparticle (e.g., “Biodegradable polymer-containing microparticles” on Top of Page 86 of English translation).
The microparticles are described as “generally spherical” or “substantially spherical” and have a diameter of greater than about 1 μm and less than about 100 μm (e.g., Bottom of Page 75, Bottom of Page 418, Bottom of Page 419 of English translation).
The microparticles are suspended in a pharmaceutically acceptable carrier, present from about 0.5% to about 95% by weight, and examples include, but are not limited to, hyaluronic acid and sodium hyaluronate (e.g., Middle of Page 415 of English translation).
Yang et al do not teach the hyaluronic acid as a mixture of hyaluronic acid having a weight average molecular weight of 1,000,000 g/mol to 3,000,000 g/mol, ammonium-substituted hyaluronic acid having a weight average molecular weight of 300,000 g/mol to 1,000,000 g/mol, and a hyaluronic acid oligomer having an average molecular weight of less than 8,000 g/mol.
These deficiencies are made up for in the teachings of Hu et al, Liu et al, and Hayami.
Hu et al teach that hyaluronic acid is widely present in connective tissue, eyeball vitreous, intercellular, synovial fluid, cornea, and bacterial walls of humans and animals and is one of the best moisturizing agents (See entire document, e.g., “Background” on Page 2 of English translation). Hu et al teach that low molecular weight, oligomeric hyaluronic acid (700-3,000 Da = 700-3,000 g/mol) is used in fields including medicine and can promote the generation of capillary vessels, promote wound healing, and promote the synthesis of endothelial cell collagen (e.g., Page 4 Lines 13-21 of English translation). Hu et al teach a method for preparing the oligomeric hyaluronic that is simple in process, low in cost, and suitable for large-scale industrial production (e.g., Page 4 Lines 18-19 of English translation).
Liu et al teach novel use of cationized hyaluronic acid with quaternary ammonium-containing group for ocular drug delivery, wherein the cationized hyaluronic acid with quaternary ammonium-containing group shows improved moisturization and because of its adsorption property on an ocular surface, prolongs the retention time and improves the corneal permeation and accumulation of the drug to be delivered (See entire document, e.g., Page 133 Col. 2 Par. 1-Page 134 Col. 1 Par. 2). Although Liu et al teach that the cationized hyaluronic acid is synthesized from hyaluronic acid and the cationic reagent glycidyl trimethylammonium chloride (e.g., Page 135 Col. 2 Last Par.), Liu et al do not provide further details of the synthesis including molecular weights of reactant or product. However, Hayami teaches the synthesis of the same cationized hyaluronic acid from raw material hyaluronic acid and/or salt thereof and cationizing agents including glycidyl trimethylammonium chloride, wherein using raw material hyaluronic acid and/or salt thereof with an average molecular weight of preferably 1 million to 2 million results in cationized hyaluronic acid having an average molecular weight of more preferably 50,000 to 1,500,000 (See entire document, e.g., Par. spanning Pages 4-5 of English translation, Examples).
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 Yang et al, Hu et al, Liu et al, and Hayami, to provide a microparticle composition in the form of “generally spherical” or “substantially spherical” microparticles having a diameter of greater than about 1 μm and less than about 100 μm comprising PLA as biodegradable polymer and PLA-PEG as hydrophobic polymer covalently bound to a hydrophilic biodegradable polymer, wherein PLA may be PLLA (poly-L-lactic acid), racemic PLLA (poly-L-lactic acid), PDLA (poly-D-lactic acid), and PDLLA (poly-DL-lactic acid), or mixtures thereof, and wherein PLA has a molecular weight of about 30 to 60 kD, suspended in a pharmaceutically acceptable carrier being the combination of hyaluronic acid having an average molecular weight of 1 million to 2 million, oligomeric hyaluronic acid having a molecular weight of 700-3,000 g/mol, and cationized hyaluronic acid with quaternary ammonium-containing group having an average molecular weight of 50,000 to 1,500,000 synthesized from hyaluronic acid having an average molecular weight of 1 million to 2 million and glycidyl trimethylammonium chloride, wherein the microparticle comprises the PLA biodegradable polymer at least about 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9%, comprises the PLA-PEG hydrophobic polymer covalently bound to a hydrophilic biodegradable polymer from about 0.5% to about 10%, and comprises the combination of hyaluronic acid having an average molecular weight of 1 million to 2 million, oligomeric hyaluronic acid having a molecular weight of 700-3,000 g/mol, and cationized hyaluronic acid with quaternary ammonium-containing group having an average molecular weight of 50,000 to 1,500,000 synthesized from hyaluronic acid having an average molecular weight of 1 million to 2 million and glycidyl trimethylammonium chloride as pharmaceutically acceptable carrier from about 0.5% to about 95% by weight, wherein the microparticle composition further comprising an effective amount of a pharmaceutically active compound is used to treat an ocular or other disorder that may benefit from topical or local delivery to the eye, wherein the disorder may be of the cornea, conjunctiva, aqueous humor, iris, ciliary body, phacoscleral, choroid, retinal pigment epithelium, neuroretina, optic nerve, or vitreous humor.
One of ordinary skill in the art would have been motivated to include oligomeric hyaluronic acid having a molecular weight of 700-3,000 g/mol as the pharmaceutically acceptable carrier because Hu et al teach that oligomeric hyaluronic acid having a molecular weight of 700-3,000 g/mol can be used in the field of medicine and can promote the generation of capillary vessels, promote wound healing, and promote the synthesis of endothelial cell collagen and Hu et al offer a method for preparing the oligomeric hyaluronic that is simple in process, low in cost, and suitable for large-scale industrial production. These advantages would be useful to incorporate into the teaching of Yang et al because Yang et al teach the microparticle composition comprising an effective amount of a pharmaceutically active compound for treating an ocular or other disorder that may benefit from topical or local delivery to the eye, wherein the disorder may be of the cornea, conjunctiva, aqueous humor, iris, ciliary body, phacoscleral, choroid, retinal pigment epithelium, neuroretina, optic nerve, or vitreous humor.
One of ordinary skill in the art would have been motivated to include cationized hyaluronic acid with quaternary ammonium-containing group having an average molecular weight of 50,000 to 1,500,000 synthesized from hyaluronic acid having an average molecular weight of 1 million to 2 million and glycidyl trimethylammonium chloride as the pharmaceutically acceptable carrier because Liu et al teach that the cationized hyaluronic acid with quaternary ammonium-containing group shows improved moisturization and because of its adsorption property on an ocular surface, prolongs the retention time and improves the corneal permeation and accumulation of the drug to be delivered and Hayami offer synthesis details for the cationized hyaluronic acid with quaternary ammonium-containing group. These advantages would be useful to incorporate into the teaching of Yang et al because Yang et al teach the microparticle composition comprising an effective amount of a pharmaceutically active compound for treating an ocular or other disorder that may benefit from topical or local delivery to the eye, wherein the disorder may be of the cornea, conjunctiva, aqueous humor, iris, ciliary body, phacoscleral, choroid, retinal pigment epithelium, neuroretina, optic nerve, or vitreous humor.
There would have been a reasonable expectation of success in the inclusion of the combination of hyaluronic acid having an average molecular weight of 1 million to 2 million, oligomeric hyaluronic acid having a molecular weight of 700-3,000 g/mol, and cationized hyaluronic acid with quaternary ammonium-containing group having an average molecular weight of 50,000 to 1,500,000 synthesized from hyaluronic acid having an average molecular weight of 1 million to 2 million and glycidyl trimethylammonium chloride as the pharmaceutically acceptable carrier because examples of suitable pharmaceutically acceptable carriers in the microparticle composition is taught by Yang et al as including, but not being limited to, hyaluronic acid and sodium hyaluronate, which implies compatibility of hyaluronic acid derivatives. Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use (Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945)).
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)). 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); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)). Further, 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, 456, 105 USPQ 233, 235 (CCPA 1955)).
Thus, the modified microparticle composition of Yang et al in view of Hu et al, Liu et al, and Hayami renders obvious the biodegradable polymer dispersion of instant claims 1-3, 5, 8, and 15-18.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Yang et al (as cited above) in view of Hu et al (as cited above), Liu et al (as cited above), and Hayami (as cited above) as applied to claims 1-3, 5, 8, and 15-18 above, and further in view of Rafat et al (Biomaterials, (2010), 31, 3414-3421, published April 2010, cited in Notice of References Cited dated 12/29/2025).
The modified microparticle composition of Yang et al in view of Hu et al, Liu et al, and Hayami has been discussed supra.
None of Yang et al, Hu et al, Liu et al, or Hayami provide a teaching of a suitable molecular weight for the PLA-PEG copolymer as the hydrophobic polymer covalently bound to a hydrophilic biodegradable polymer.
This deficiency is made up for in the teaching of Rafat et al.
Rafat et al teach PEG–PLA biodegradable microparticles for delivery and release of therapeutic agents to the retina, wherein the PEG–PLA used is PEG–PLA di-block polymer (PEG(1000)-b-PLA(5000)) purchased from Polysciences, Inc. (Warrington, PA), wherein the numbers in parentheses refer to the molecular weight of the segment (See entire document, e.g., Page 3415 Col. 1 Par. 2-3).
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 teaching of Rafat et al, to use PEG(1000)-b-PLA(5000) as the specific type of PLA-PEG copolymer in the modified microparticle composition of Yang et al in view of Hu et al, Liu et al, and Hayami. One of ordinary skill in the art would have been motivated to do so, and there would have been a reasonable expectation of success, because Rafat et al offer a suitable PLA-PEG copolymer for use in applications of drug delivery to the eye and Yang et al teach the compatibility of PLA-PEG copolymer, generally, as the hydrophobic polymer covalently bound to a hydrophilic biodegradable polymer. Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use (Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945)).
Thus, the modified microparticle composition of Yang et al in view of Hu et al, Liu et al, and Hayami and further in view of Rafat et al renders obvious the biodegradable polymer dispersion of instant claim 4.
Response to Applicant’s Arguments
Applicant’s arguments filed on 03/27/2026 have been considered.
Applicant argues that amended claim 1 cannot be obviously derived from the cited references applied in the prior art rejection set forth in the Office action dated 12/29/2025. Applicant argues that Hu does not disclose a formulation in which the high-molecular-weight
hyaluronic acid and the low-molecular-weight oligomeric hyaluronic acid are mixed. Applicant argues that Yang does not mention molecular weight of the hyaluronic acid and does not provide any technical teaching regarding a combined use of the hyaluronic acid and a low-molecular-weight hyaluronic acid oligomer. Applicant argues that Liu does not mention about molecular weight of the ammonium-substituted hyaluronic acid and does not provide any suggestion or teaching regarding a use of the ammonium-substituted hyaluronic acid mixed with a high-molecular-weight hyaluronic acid and a low-molecular-weight hyaluronic acid oligomer in a specific content ratio. Applicant argues that even when the teaching of Rafat is further considered, a mixture form of the ammonium-substituted hyaluronic acid, a high-molecular-weight hyaluronic acid, and a low-molecular-weight hyaluronic acid oligomer as recited in amended claim 1, cannot be suggested, and thus, even when Yang, Hu, Liu, and Rafat are considered as a whole, the specified composition properties of the hyaluronic acid mixture of amended claim 1 cannot be obviously derived.
The above arguments have been fully considered by the Examiner but are not found persuasive because, as can be seen in the new grounds of rejection under 35 USC 103 above, the teaching of Hayami cures the deficiencies of Yang et al, Hu et al, and Liu et al and the modified microparticle composition of Yang et al in view of Hu et al, Liu et al, and Hayami meets all of the limitations of amended claim 1 (See above for more details). Further, the new grounds of rejection under 35 USC 103 of claims 1-3, 5, 8, and 15-18 is based on the combined teachings of Yang et al, Hu et al, Liu et al, and Hayami and of claim 4 is based on the combined teachings of Yang et al, Hu et al, Liu et al, Hayami, and Rafat et al and not their individual teachings. 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 encouraged to refer to the above rejections under 35 USC 103 for the Examiner’s discussion of why one of ordinary skill in the art would have looked to each of the teachings of Hu et al, Liu et al, Hayami, and Rafat et al from the teaching of Yang et al and why there would have been a reasonable expectation of success in modifying the teaching of Yang et al based on each of the teachings of Hu et al, Liu et al, Hayami, and Rafat et al.
Conclusion
No claims are allowable.
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.
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/K.E.O./Examiner, Art Unit 1619
/DAVID J BLANCHARD/Supervisory Patent Examiner, Art Unit 1619
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