DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . The amendment filed on 06/16/2026 has been entered. Claims 9 and 19 are cancelled. Claims 1-8 and 10-18 are pending in this application. Claims 5-8 and 11-18 are withdrawn. Claims 1-4 and 10 are currently under examination.
Priority
This application is a 371 of PCT/CN2022/087577 04/19/2022 and claims foreign priority of CHINA 202110433689.7 filed on 04/20/2021 and CHINA 202110433699.0 filed on 04/20/2021.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 365(c) or 386(c) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. CHINA 202110433689.7 or CHINA 202110433699.0, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Claims 1 and 10 recites “the mass percentage concentration of the thiolated polysaccharide derivative in the aqueous solvent is 2% to 10%, and the thiol substitution degree of the thiolated polysaccharide derivative is 3% to 25%... 3% to 25%... hydroxyethyl hyaluronic acid, hydroxypropyl hyaluronic acid, acetyl hyaluronic acid, butyryl hyaluronic acid, aminoacetic hyaluronic acid, aminopropionic hyaluronic acid, aminobutyric hyaluronic acid, hydrazide hyaluronic acid… other hyaluronic acid derivatives”, which is not disclosed or supported by the prior-filed Application No. CHINA 202110433689.7 or CHINA 202110433699.0. Thus, the priority date of claims 1 and 10 is 04/19/2022.
Election/Restrictions
Applicant's election without traverse of Group I invention (claims 1-4 and 10) in the reply filed on 06/16/2026 is acknowledged. Claims 5-8 and 11-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention or species, there being no allowable generic or linking claim. Thus, claims 1-4 and 10 are currently under examination.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 01/11/2024 and 08/08/2025 with appropriate assertion under 37 CFR 1.98 have been considered.
Claim Objections
Claims 2 and 4 are objected to because of the following informalities: In claims 2 and 4, insert the missing phrase “wherein the hydrogel is” immediately after the recitation “claim 1,” (line 1 of claims 2 and 4” to become proper dependent claim format; also in claim 2, change the incorrect conjunction “and” (line 9), which means combination of (i) and (ii) hydrogels, to “or”. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-4 and 10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claims 3, 4, and 10 depend from claim 1.
Claims 1 and 2 recite “derivative”, which is not specifically defined. It is not clear how the claimed structure is derivatized. Thus, the metes and bounds of the recitation cannot be determined.
Claims 1 and 2 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential structural cooperative relationships of elements, such omission amounting to a gap between the necessary structural connections. See MPEP § 2172.01. The omitted structural cooperative relationships are: Claim 1 recites “the polysaccharide derivative is selected from” (lines 4 to 5 of claim 1). However, the selected derivatives do not contain the required “thiolated” component in the preceding clause. Claim 2 recites “the hyaluronic acid derivative is selected from” (line 5) and “the chitin/chitosan derivative is selected from” (line 4 on page 3 of 10). Again, the selected derivatives do not have the required “thiolated” component in the preceding clause.
Taken together, Applicant is advised to insert the phrase “with grafted side chain groups”, supported by the Specification, immediately after the recitations “a thiolated polysaccharide derivative” (line 1 of claim 1), “the polysaccharide derivative” (line 4 of claim 1), “a thiolated hyaluronic acid derivative” (line 2 of claim 2), “the hyaluronic acid derivative” (line 5 of claim 2), “a thiolated chitin/chitosan derivative” (line 1 on page 3 of 10), and “the chitin/chitosan derivative” (line 4 on page 3 of 10), respectively; and to insert the phrase “component of” immediately after the recitation “and wherein the” (line 4 of claim 1; line 5 of claim 2; line 4 on page 3 of 10, respectively).
Claim Rejections - 35 USC § 102/103
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(I) Claims 1-4 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Shu et al. (EP 2614828, July 17, 2013, hereinafter referred to as Shu ‘828) incorporated by Shu et al. (Biomacromolecules 3, 1304-1311, 2002, hereinafter referred to as Shu ‘2002) as evidenced by Santhanam et al. (J Biomed Mater Res Part A 2015:103A:2300–2308, hereinafter referred to as Santhanam ‘2015, also listed in IDS filed on 08/08/2025).
With regard to structural limitations “A hydrogel (or suitable for use as an intraocular vitreous substitute) formed from a thiolated polysaccharide derivative and an aqueous solvent (or water, physiological saline, or phosphate buffer), wherein the mass percentage concentration of the thiolated polysaccharide derivative in the aqueous solvent is 2% to 10% (or 2.5% to 6%), and the thiol substitution degree of the thiolated polysaccharide derivative is 3% to 25% (or 3% to 20%), and wherein the polysaccharide derivative is selected from the group consisting of aminopropionic hyaluronic acid, hydrazide hyaluronic acid, andr other hyaluronic acid derivatives” (claims 1-4):
Shu ‘828 disclosed Example 1: Preparation of the mercapto-modified hyaluronic acid derivative. The preparation was made according to the method disclosed by Shu et al. in Biomacromolecules, 3, 1304, 2002. Dithiodipropionic dihydrazide was added to a solution of hyaluronic acid (11.9 g) in distilled water. A certain amount of 2-ethyl-3-(3-dimethylaminepropyl) carbodiimide hydrochloride (EDCI) was added. Then 100 g dithiothreitol and an amount of 1.0 mol/L sodium hydroxide were added with stirring (page 7/16, [0044, 0045]). Shu ‘2002 (incorporated by reference here) disclosed Figure 2. Synthetic scheme and structure of thiolated HA derivative:
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. Gelation of Thiolated HA Solutions: HA-DTBH and HA-DTPH were dissolved in Dulbecco’s phosphate-buffered saline (DPBS) to give 3.0% (w/v) solutions under N2 protection. After exposure to air at room temperature for 15 or 30 min, a gel is formed if no fluidity was visually observed (page 1306, Figure 2; left col., para. 2). Shu ‘828 also disclosed Example 3: Sodium salt of Sulfo-N-hydroxy succinimide (Sulfo-NHS), cystamine dihydrochloride (CYS) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDCI) was added to a solution of hyaluronic acid (10 g) in distilled water (1 L) respectively. Then 50 g dithiothreitol and an amount of 1.0 mol/L sodium hydroxide were added with stirring. Example 4: Preparation of the disulfide-bond cross-linked hyaluronic acid hydrogel. Two kinds of mercapto-modified hyaluronic acid derivative prepared in Example 1 (having a degree of mercapto-modification of 2.33% and 4.18%, and indicated as Nos. 4 and 6 in Table 1, respectively) were dissolved to give a 10 mg/ml solution, a 15 mg/ml solution and a 20 mg/ml solution, respectively, with the pH values adjusted to 7.4. The above solutions (2 ml) were sealed respectively, and stand at room temperature for one week. Thus the solutions lose their fluidity and form the cross-linked hydrogels. Example 9: Hydrogel 1: The mercapto-modified hyaluronic acid derivative prepared in Example 3 (having a degree of mercapto-modification of 13.5%, and indicated as No. 1 in Table 3) was dissolved to give a 10 mg/ml solution, with the pH value adjusted to 7.4. 2 ml of the above solution was transferred into a 10 m/ glass bottle and sealed, and stand at room temperature for 10 days. Thus the solution loses its fluidity and forms the cross-linked hydrogel (pages 8/16 to 9/16, [0054, 0055, 0059, 0060, 0071, and 0072]). The mercapto-modified biocompatible macromolecule derivative is dissolved in water to obtain a solution of a suitable concentration (usually 0.2%-5.0%), which is adjusted to a specific pH value (usually neutral), and then the solution is filled into the injectable container and sealed, with the mercapto group gradually forming the disulfide-bond mainly under the action of oxidation of the dissolved oxygen in the solution, making the solution gradually gelatinated (page 5/16, [0028]). Santhanam ‘2015 (cited here as evidence for disulfide crosslink chemistry of Example 3 and suitability as a permanent vitreous substitute) disclosed Figure 1. Carbodiimide crosslinking reaction of HA and Cys with EDC and NHS:
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. The formulations needed to synthesize HA hydrogels of a specified degree of amidation and thus thiolation. DoE predicts the optimal formulations for carrying out the amidation reaction with the help of the polynomial model equation for any specified degree of amidation. For instance, to amidate 7.5 mol % of HA (based on repeat units) with minimal side reactions. The chemical modification of HA plays a significant role in designing the scaffolds for its use in applications such as tissue engineering, targeted drug delivery via thiol-modified-HA coated gold nanoparticles, and permanent vitreous substitute with in vivo gelling properties. Pre-determining the degree of derivatization of HA is critical for defining the mechanical properties of the scaffolds specific to its application (page 2303, Figure 1; page 2307, right col., para. 2 and 3).
Thus, these teachings of Shu ‘828 incorporated by Shu ‘2002) and evidenced by Santhanam ‘2015 anticipate Applicant’s claims 1-4.
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.
(II) Claims 1-4 and 10 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Santhanam et al. (J Biomed Mater Res Part A 2015:103A:2300–2308, hereinafter referred to as Santhanam ‘2015, also listed in IDS filed on 08/08/2025).
With regard to structural limitations “A hydrogel (or an intraocular vitreous substitute) formed from a thiolated polysaccharide derivative and an aqueous solvent (or water or physiological saline), wherein the mass percentage concentration of the thiolated polysaccharide derivative in the aqueous solvent is 2% to 10% (or 2.5% to 6%), and the thiol substitution degree of the thiolated polysaccharide derivative is 3% to 25% (or 3% to 20%), and wherein the polysaccharide derivative is selected from other hyaluronic acid derivatives” (claims 1-4 and 10):
Santhanam ‘2015 disclosed Figure 1. Carbodiimide crosslinking reaction of hyaluronic acid (HA) and cystamine (Cys) with EDC and NHS:
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. The final product of the reaction, amide-substituted HA, was reduced with DTT, purified with DI water free of oxygen (through nitrogen bubbling) at acidic pH and lyophilized to obtain a white fluffy, fibrous solid. The formulations needed to synthesize HA hydrogels of a specified degree of amidation and thus thiolation. DoE predicts the optimal formulations for carrying out the amidation reaction with the help of the polynomial model equation for any specified degree of amidation. For instance, to amidate 7.5 mol % of HA (based on repeat units) with minimal side reactions. The chemical modification of HA plays a significant role in designing the scaffolds for its use in applications such as tissue engineering, targeted drug delivery via thiol-modified-HA coated gold nanoparticles, and permanent vitreous substitute with in vivo gelling properties. Pre-determining the degree of derivatization of HA is critical for defining the mechanical properties of the scaffolds specific to its application (page 2303, Figure 1; right col., para. 2; page 2307, right col., para. 2 and 3). HA hydrogel is useful in ophthalmic surgeries as a vitreous substitute after vitrectomy (page 2300, left col., para. 1).
Thus, these teachings of Santhanam ‘2015 anticipate or, in an alternative, are obvious to Applicant’s claims 1-4 and 10 because (a) the thiolated amide-modified HA plays a significant role in designing the scaffolds for its use in permanent vitreous substitute with in vivo gelling properties, and (b) lyophilized thiolated amide-modified HA is dissolved in acidic water in an effective amount for a specific application, including as a permanent vitreous substitute, described above.
Conclusion
No claims are allowed.
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/YIH-HORNG SHIAO/Primary Examiner, Art Unit 1691
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