DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on May 18, 2026, has been entered.
Claim Disposition
3. Claims 2-3, 6 and 9 were canceled. Claims 1, 4-5, 7-8 and 10-15 are pending and are under examination.
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.
4. 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.
5. Claim(s) 1, 4 and 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Huang et al. (Bioactive Materials, 2017, of record in the application) in view of Ibrahim et al. (of record in the application) and Motiel et al. (WO 2022012703, July 13, 2020).
Huang et al. discloses a hydrogel comprising hyaluronic acid polymers at least partially crosslinked with fibrinogen molecules (a novel HA-based hydrogel was developed via the in situ supramolecular assembly based on knob-hole interactions between fibrinogen and knob-grafted HA synthesized by coupling GPRPAAC peptides to methacrylated HA via Michael addition reaction which is known in the art as a click reaction under certain conditions (see page 254, column 1, fourth paragraph, see abstract). Huang et al. also discloses the hydrogel of claim 1, wherein the hydrogel does not comprise collagen (materials do not comprise collagen, see page 254, column 2, first paragraph). Huang et al. does not explicitly teach wherein the hyaluronic acid polymer is partially crosslinked with glycidyl methacrylate. Ibrahim et al. is in the field of hyaluronic acid conjugation (the present paper studies photo-crosslinked hydrogels containing glycidyl methacrylate-derivatized bio-inert high molecular weight HA and a bioactive HA oligomer mixture, see abstract) and teaches wherein the hyaluronic acid polymer is crosslinked with glycidyl methacrylated (the present paper studies photo-crosslinked hydrogels containing glycidyl methacrylate-derivatized bio-inert high molecular weight HA and a bioactive HA oligomer mixture, see abstract). The invention of claim 4 is known because Huang et al. discloses the above conjugate (see page 254 and abstract). In addition, modified Huang et al. discloses a method for producing a hydrogel, comprising combining the composition of claim 4 with an effective amount of a photo-initiator and ultraviolet light to crosslinked unconjugated methacrylate sites through free-radical polymerization (it is known that the crosslinking of the fibrinogen/MA-HA hydrogels was based on the free radical polymerization of MA-HA with the addition of the photo-initiator 2959 and under UV irradiation (see page 255, col. 1, second paragraph). In addition, Motiel et al. teach hydrogel which forms a drug delivery system……the second component is a hyaluronic acid-based hydrogel forming a support structure for mesenchymal stem cells……. (see abstract). Motiel et al. also teach that “Its preparation comprises the following steps: separate modification of hydroxyethyl chitosan and hyaluronic acid with glycidyl methacrylate to obtain hydroxyethyl chito san-grafted glycidyl methacrylate and hyaluronic acid-grafted glycidyl methacrylate. Glycidyl methacrylate grafted with hydroxyethyl chitosan is photochemically polymerized to obtain a hydroxyethyl chitosan hydrogel of the first network, and the hydroxyethyl chitosan hydrogel is lyophilized, impregnated in an aqueous photo-initiator solution and glycidyl methacrylate grafted with hyaluronic acid and photochemically polymerized; thereby obtaining a hydroxyethyl chitosan hydrogel….” (see paragraph 6).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to arrive at the claimed invention as a whole because the combined teaching of the references renders the claims as obvious. The references are considered to be analogous art, thus motivation to combine exists. It would have been obvious to one of ordinary skill in the art to modify Huan et al. with the teaching of Ibrahim and Motiel et al., with the motivation for doing so being that glycidyl methacrylate has little effect on the cellular response (these results demonstrate that cell response to HA/HA-o is not altered by their methacrylation and photo-crosslinking into a hydrogel, see abstract) thereby allowing the use of other potential methacrylates in the crosslinking.
Moreover, the Supreme Court pointed out in KSR, “a patent composed of several elements is not proved obvious merely by demonstrating that each of its elements was, independently, known in the prior art.” KSR, 127 S. Ct. at 1741. The Court thus reasoned that the analysis under 35 U.S.C. 103 "need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the “inferences and creative steps that a person of ordinary skill in the art would employ.” Id. at 1741. The Court further advised that “[a] person of ordinary skill is…a person of ordinary creativity, not an automation.” Id. at 1742. Therefore, the claimed invention was obvious to make and use at the time the invention was made and was prima facie obvious.
6. Claim(s) 1, 4-5 and 7-8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Huang et al. (Bioactive Materials, 2017, of record in the application) in view of Ibrahim et al. (of record in the application) and Yuan et al. (Adv. Mater. Res., 2015, of record in the application) and Motiel et al. (WO 2022012703, July 13, 2020).
The teaching of Huang et al. and Motiel et al. is set forth above. Huang et al. teach the composition set forth in claim 4 and the hydrogel of claim 1, wherein the fibrinogen molecule is conjugated to the methacrylate hyaluronic acid monomer (supramolecular assembly based on knob-hole interactions between fibrinogen and knob-grafted HA, see abstract). Huang et al. fails to explicitly disclose wherein the fibrinogen molecule is conjugated to the glycidyl methacrylate hyaluronic acid monomer which is taught by Motiel et al. and Huang et al. does not teach this occurs by a click chemistry. However, Yuan is in the art of hyaluronic acid hydrogels (see page 286, first paragraph) and teaches conjugation of a glycidyl methacrylate hyaluronic acid monomer by a click chemistry reaction (HA will form hydrogel structure by adding crosslinker such as a glycidyl methacrylate and adipic acid dihydrazide, page 286, first paragraph).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to arrive at the claimed invention as a whole because the combined teaching of the references renders the claims as obvious. The references are considered to be analogous art, thus motivation to combine exists.
It would have been obvious to one of ordinary skill in the art at the time of the invention to modify Huang with the teaching of Yuan and Motiel et al., to conjugate fibrinogen to hyaluronic acid via a glycidyl methacrylate hyaluronic acid monomer. The motivation for doing so would be to use a methacrylate that allows the most biocompatibility and desired cellular response. Further, Huang teach a photo initiator (hydrogels were also prepared according to the similar procedure with fibrinogen solution of 200 mg/ml and treated under ultraviolet irradiation of 3 mins with addition of photo initiator 2959, see page 255, col. 1, second paragraph). Note also that Huang meets the limitation with claim 7 and provides the photoinitiated (see page 255 col. 1, second paragraph).
Moreover, the Supreme Court pointed out in KSR, “a patent composed of several elements is not proved obvious merely by demonstrating that each of its elements was, independently, known in the prior art.” KSR, 127 S. Ct. at 1741. The Court thus reasoned that the analysis under 35 U.S.C. 103 "need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the “inferences and creative steps that a person of ordinary skill in the art would employ.” Id. at 1741. The Court further advised that “[a] person of ordinary skill is…a person of ordinary creativity, not an automation.” Id. at 1742. Therefore, the claimed invention was obvious to make and use at the time the invention was made and was prima facie obvious.
7. Claim(s) 1, 4 and 10-13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Huang et al. (Bioactive Materials, 2017, of record in the application) in view of Guangzhou Beogene Biotechnology (CN 111214699, of record in the application), and Motiel et al. (WO 2022012703, July 13, 2020).
Huang et al. discloses a hydrogel comprising hyaluronic acid polymers at least partially crosslinked with fibrinogen molecules (a novel HA-based hydrogel was developed via the in situ supramolecular assembly based on knob-hole interactions between fibrinogen and knob-grafted HA synthesized by coupling GPRPAAC peptides to methacrylated HA via Michael addition reaction (see page 254, column 1, fourth paragraph, see abstract). Huang et al. also discloses the hydrogel of claim 1, wherein the hydrogel does not comprise collagen (materials do not comprise collagen, see page 254, column 2, first paragraph). Huang et al. does not explicitly teach wherein the hyaluronic acid polymer is partially crosslinked with glycidyl methacrylate. The invention of claim 4 is known because Huang et al. discloses the above conjugate (see page 254 and abstract). In addition, modified Huang et al. discloses a method for producing a hydrogel, comprising combining the composition of claim 4 with an effective amount of a photo-initiator and ultraviolet light to crosslinked unconjugated methacrylate sites through free-radical polymerization (it is known that the crosslinking of the fibrinogen/MA-HA hydrogels was based on the free radical polymerization of MA-HA with the addition of the photo-initiator 2959 and under UV irradiation (see page 255, col. 1, second paragraph). Huang fails to teach a method for treating a subject with peripheral nerve injury, (but teaches the hydrogel used) comprising implanting the hydrogel at the site of the injury to promote neural regeneration. However, Guangzhou is in the field of hyaluronic acid hydrogels (the invention relates to a hydrogel for repairing peripheral nerve injury). The hydrogel contains the following components in percentages by mass 0.2%-0.6% of hyaluronic acid, (see abstract) and teaches a method for treating a subject with peripheral nerve injury (see abstract) comprising implanting a hydrogel containing hyaluronic acid at the site of the injury to promote neural regeneration (can be used for injection administration, see abstract), improve the bioavailability of NGF by locally releasing it in lesion (see paragraph [0004]) . With regard to the recitation of the peripheral nerve injury involves a traumatic accident, a vascular disease, or tumor excision, a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to distinguish the claimed invention from the prior art. In the prior art is capable of performing the intended use it meets the claim. In this case the method of a modified Huang would have enabled treatment of a peripheral nerve injury involving a traumatic accident, a vascular disease or tumor excision. The same reason can be applied to the recitation of wherein the vascular disease is a peripheral arterial disease and diabetes. In addition, Motiel et al. teach hydrogel which forms a drug delivery system……the second component is a hyaluronic acid-based hydrogel forming a support structure for mesenchymal stem cells……. (see abstract). Motiel et al. also teach that “Its preparation comprises the following steps: separate modification of hydroxyethyl chitosan and hyaluronic acid with glycidyl methacrylate to obtain hydroxyethyl chito san-grafted glycidyl methacrylate and hyaluronic acid-grafted glycidyl methacrylate. Glycidyl methacrylate grafted with hydroxyethyl chitosan is photochemically polymerized to obtain a hydroxyethyl chitosan hydrogel of the first network, and the hydroxyethyl chitosan hydrogel is lyophilized, impregnated in an aqueous photo initiator solution and glycidyl methacrylate grafted with hyaluronic acid and photochemically polymerized; thereby obtaining a hydroxyethyl chitosan hydrogel….” (see paragraph 6).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to arrive at the claimed invention as a whole because the combined teaching of the references renders the claims as obvious.
It would be obvious to one of ordinary skill in the art to modify Huang with the teaching of Guangzhou to provide precise and targeted treatment of the effective peripheral nerves and Motiel et al. which provides crosslinked with glycidyl methacrylate. Further, we regard to promote neural regeneration a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to distinguish the claimed invention from the prior art. If the prior art is capable of performing the intended use, it meets the claim. In this case, the hydrogel of Huang, modified and implanted as taught by Guangzhou, is capable of providing nerve growth factor effective to promote neural regeneration. In addition, the references are considered to be analogous art, another motivation to combine.
Moreover, the Supreme Court pointed out in KSR, “a patent composed of several elements is not proved obvious merely by demonstrating that each of its elements was, independently, known in the prior art.” KSR, 127 S. Ct. at 1741. The Court thus reasoned that the analysis under 35 U.S.C. 103 "need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the “inferences and creative steps that a person of ordinary skill in the art would employ.” Id. at 1741. The Court further advised that “[a] person of ordinary skill is…a person of ordinary creativity, not an automation.” Id. at 1742. Therefore, the claimed invention was obvious to make and use at the time the invention was made and was prima facie obvious.
8. Claim(s) 1, 4, 10 and 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Huang et al. (Bioactive Materials, 2017, of record in the application) in view of Guangzhou Beogene Biotechnology (CN 111214699, of record in the application) and Jin et al. (of record in the application), and Motiel et al. (WO 2022012703, July 13, 2020).
The teaching of Huang et al., Guangzhou and Motiel et al. are set forth above. Huang et al. does not teach wherein the hydrogel is wrapped in a nerve guidance conduit prior to implantation. However, Huang et al. teaches the hydrogel comprising hyaluronic acid polymers utilized. Jin et al. is in the field of hydrogel treatments for nerve injury (peripheral nerve repair in rats using composite hydrogel-filled aligned nanofiber conduits with incorporated nerve growth factor, see title) and teaches wherein the hydrogel is wrapped in a nerve guidance conduit prior to implantation (aligned nanofiber tubular conduits with 12-mm length x 1.1 mm internal diameter and 200 micrometer wall conduit thickness, were filled with 4C+4 H hydrogel, with or without 100 ng/mL. NGF and incubated at 37°C for one hour to allow gelation…. The autograph and conduit graphs were sewn into place using 8-0 nylon sutures (see page 2139, col. 2, fourth paragraph to page 2140, col. 1, first paragraph).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to arrive at the claimed invention as a whole because the combined teaching of the references renders the claims as obvious.
It would be obvious to one of ordinary skill in the art to modify Huang with the teaching of Jin et al. with the motivation for doing so being to add the conduit as is previously done in the art to better assist in the repair of nerve injuries. In addition, the references are considered to be analogous art, another motivation to combine.
Moreover, the Supreme Court pointed out in KSR, “a patent composed of several elements is not proved obvious merely by demonstrating that each of its elements was, independently, known in the prior art.” KSR, 127 S. Ct. at 1741. The Court thus reasoned that the analysis under 35 U.S.C. 103 "need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the “inferences and creative steps that a person of ordinary skill in the art would employ.” Id. at 1741. The Court further advised that “[a] person of ordinary skill is…a person of ordinary creativity, not an automation.” Id. at 1742. Therefore, the claimed invention was obvious to make and use at the time the invention was made and was prima facie obvious.
9. Claim(s) 1, 4, 10 and 14-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Huang et al. (Bioactive Materials, 2017, of record in the application) in view of Guangzhou Beogene Biotechnology (CN 111214699, of record in the application), Jin et al. (of record in the application) and Yi et al. (of record in the application).
The teaching of Huang et al., Guangzhou, Jin et al. and Motiel et al. are set forth above. Huang et al. does not teach wherein the nerve guidance conduit comprises decellularized porcine small intestine submucosa. Yi teaches wherein nerve guidance can do it comprises decellularized porcine small intestine submucosa (see abstract), a part of the small intestine….. Was excised and all mesenteric tissues were removed (see page 66, first col. and first full paragraph).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to arrive at the claimed invention as a whole because the combined teaching of the references renders the claims as obvious.
It would be obvious to one of ordinary skill in the art to modify Huang to use the nerve guidance conduit that comprise decellularized porcine small intestine submucosa as taught by Yi with the motivation for doing so being to add the conduit as is previously done in the art to use the biomaterial that would have more beneficial effects in vivo or less adverse effects. In addition, the references are considered to be analogous art, another motivation to combine.
Moreover, the Supreme Court pointed out in KSR, “a patent composed of several elements is not proved obvious merely by demonstrating that each of its elements was, independently, known in the prior art.” KSR, 127 S. Ct. at 1741. The Court thus reasoned that the analysis under 35 U.S.C. 103 "need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the “inferences and creative steps that a person of ordinary skill in the art would employ.” Id. at 1741. The Court further advised that “[a] person of ordinary skill is…a person of ordinary creativity, not an automation.” Id. at 1742. Therefore, the claimed invention was obvious to make and use at the time the invention was made and was prima facie obvious.
Response to Arguments
10. Applicant’s comments have been considered in full. Withdrawn objections/rejections will not be discussed herein as applicant’s comments are moot. Note that new art rejections have been instituted for the reasons stated above.
Conclusion
11. No claims are presently allowable.
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/HOPE A ROBINSON/Primary Examiner, Art Unit 1652
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