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 .
Detailed Action
This application is a national stage application of PCT/CN2023/071208, filed January 9, 2023, which claims benefit of foreign application CN202210042774.5, filed January 14, 2022. Claims 13-26 are pending in this application and examined on the merits herein. Applicant’s preliminary amendment submitted July 9, 2024, is acknowledged wherein claims 1-12 are canceled and new claims 13-26 are introduced.
Drawings
The drawings are objected to because they are not entirely legible. The combination of small font size and low resolution in figures 1 and 2 makes it impossible to interpret all of the text appearing in the figures. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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.
Claims 13-26 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (US pre-grant publication 2010/0316682, cited in PTO-892) in view of Wei et al. (US pre-grant publication 2020/0147262, cited in PTO-892)
Independent claim 13 is directed to a hyaluronic acid derivative which is derivatized by an ether-linked methoxy-polyethyleneglycol (mPEG) at the 6- position. The conjugate is further defined as having a degree of polymerization of 100-8000 HA disaccharides and 40-4600 PEG monomers. Dependent claim 14 more narrowly defines the degrees of polymerization of the HA and mPEG, and claims 15-17 and 19 more specifically define the structure of the linkage between the two moieties as a glycidyl ether.
Chen et al. discloses a biodegradable HA derivative comprising a hyaluronic acid esterified with a modifying moiety containing a prepolymer. (p. 1 paragraph 18) The HA has a preferred molecular weight of 2-3500 kDa. (p. 3 paragraph 67) In one embodiment the prepolymer can be a hydrophilic prepolymer such as polyethylene glycol, (p. 4 paragraph 75) and can have a molecular weight of 200-50000. (p. 4 paragraph 82) In a specific example (p. 11 example B15 paragraph 178) a mpeg having mw of 5000 Da is grafted onto a HA having a mw of 1000000 Da. Based on a monomer mw of 44 for PEG, the mPEG has a dp of about 113. Based on a mw of 378 for HA disaccharide, the HA has a disaccharide dp of about 2645. Therefore the resulting conjugate is the same as the conjugate claimed in present claims 13-17 and 19 except that the mPEG is attached to the 6-OH of the HA by an ester or urethane linkage rather than a glycidyl ether.
However, Wei et al. discloses epoxide-functionalized PEG crosslinkers having an epoxymethylene reactive group at each end. (p. 1 paragraphs 6-10, p. 2 paragraph 24) Wei et al. further discloses a crosslinking method for HA comprising dissolving the HA in aqueous solution with the PEG epoxide, and reacting the mixture to produce a crosslinked HA wherein the PEG is linked to the 6-OH positions of the HA by a glycidyl ether. (p. 4 paragraphs 73-81)
It would have been obvious to one of ordinary skill in the art at the time of the invention to make HA-mPEG conjugates as described by Chen et al. using a glycidyl ether linkage to attach the mPEG to the HA in place of the linkage used in Chen’s disclosure. One of ordinary skill in the art would have seen the different linkage chemistries described by Chen and Wei as being alternatives usable for the same purpose of linking a PEG to the 6- position of HA.
Regarding present claim 18, the HA used in example B15 of Wei is described as a “quaternary ammonium” salt. According to preparative example 1 on p. 5 of Wei, this quaternary ammonium salt is in fact prepared with a tetrabutylammonium cation, thereby infringing the limitation of this claim. Regarding the process recited in present claim 20, the steps recited in this process are substantially the same as those recited in paragraph 74 on p. 4 of Chen, involving dissolving both the HA and the PEG epoxide in an aqueous alkaline solution and reacting them together. Therefore it would have been obvious to one of ordinary skill in the art to perform the steps of dissolving the two components into alkaline solution and stirring the two solutions together, in any particular order.
Regarding claim 21, p. 4 paragraph 75 describes adding an acid to neutralize the product solution. Regarding claim 23, p. 6 paragraph 113 of Wei describes a molar ratio of 0.2:1. Regarding claim 22, p. 3 paragraph 64 of Wei describes HA to alkaline solution ratios between 1:5 and 1:30. Regarding claim 24, while the prior art does not specifically disclose what an appropriate reaction time is for the claimed reaction, one of ordinary skill in the art would necessarily recognize the need to react the epoxide with the HA for an appropriate amount of time, and therefore would have regarded reaction time as a result-effective variable, motivating them to determine the appropriate reaction time to use in the reaction described by Wei.
Regarding claims 25 and 26, these claims refer to intended uses for the HA derivative rather than specific methods of use involving actual process steps. Therefore the intended use limitations merely require that the claimed HA derivative could potentially be used for the recited purposes, and therefore do not meaningfully distinguish the claimed subject matter from the prior art.
Therefore the invention taken as a whole is prima facie obvious.
Conclusion
No claims are allowed in this action.
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/ANDREA OLSON/ Primary Examiner, Art Unit 1693 10/9/2026
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