DETAILED ACTION
Status of the Claims
Claims 1-10 are pending in the instant application. Claims 8 and 10 have been withdrawn based upon Restriction/Election as discussed below. Claims 1-7 and 9 are being examined on the merits in the instant application.
Advisory Notice
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Restriction/Election
Applicant's election with traverse of Group I drawn to methods of making a composite hydrogel composition, currently claims 1-7 and 9 in the reply filed on 09/22/2025 is acknowledged. The traversal is on the ground(s) that “It is also respectfully submitted that the subject matter of all claims is sufficiently related that a thorough search for the subject matter of any one Group of claims would encompass a search for the subject matter of the remaining claims. Thus, it is respectfully submitted that the search and examination of the entire application could be made without serious burden.”. This is not found persuasive because a search burden exists because (1) The inventions have acquired a separate status in the art in view of their different classification, (2) The inventions have acquired a separate status in the art do to their recognized divergent subject matter, and/or (3) The inventions required different field of search (e.g., searching different classifications or electronic resources, or employing different search strategies or search queries). Additionally, it is noted that the product claims 8 & 10 (Group II) are product-by-process claims not limited by the method steps in Group I (MPEP §2113).
The requirement is still deemed proper and is therefore made FINAL.
Claims 8 and 10 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected subject matter, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 09/22/2025.
Priority
The U.S. effective filing date has been determined to be 09/07/2022, the filing date of the instant application. Applicant's claim for a foreign priority date of, 06/16/2022, the filing date of document CHINA 2022106799718, is acknowledged, however no certified copy or English translation of the foreign priority document CHINA 2022106799718 has been provided. Accordingly, foreign priority to this document is cannot be afforded at this time.
Information Disclosure Statement
No Information Disclosure Statements have been filed in the instant application. Applicants are reminded of their duty to disclose patents and publications relevant to the patentability of the instant claims. Applicant is reminded of the requirements of 37 CFR 1.56 and Li Second Family Limited Partnership v. Toshiba Corp., 56 USPQ2d 1681 (Fed. Cir. 2000); accord McKesson Information Solutions, Inc. v. Bridge Medical, Inc. 487 F.3d 897, 913. (Fed.Cir.2007).
Claim Objections
Claims 1 and 4 are objected to because of the following informalities: each claim recites “lithium phenyl-2,4,6-trimethylbenzoylpho-sphinate (LAP)” (claim 1, step (2), and claim lines 2-3), where the correct chemical name should be “lithium phenyl (2,4,6-trimethylbenzoyl) phosphinate (LAP)” or “lithium phenyl-2,4,6-trimethylbenzoyl-phosphinate (LAP)” (see Nguyen et al.1 and Han et al.2). Appropriate correction is required.
Claim 2 is objected to because the claim recites “adding 1-ethyl-3-(3- dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) to the solution for activation at 37°C; after the activation, dissolving L-glutamic acid hydrochloride in the solution at 37°C, and continuing to stir the solution at 37°C for sufficient reaction; and preferably, mass volume concentrations of the hyaluronic acid, the 1-ethyl-3-(3- dimethylaminopropyl) carbodiimide hydrochloride, the N-hydroxysuccinimide and the L- glutamic acid hydrochloride in the solution system are 1%, 0.72%, 0.44% and 1.46%, respectively.” the abbreviations EDC and NHS are recited in line 4, however they are never utilized in any of the claims, rather Applicant later uses the full chemical name. Applicant should either use the abbreviations EDC and NHS or delete them from the claims. Appropriate correction is required.
Claim 4 is objected to because the claim depends from claim 1 reciting “(2) dissolving a photoinitiator lithium phenyl-2,4,6-trimethylbenzoylpho-sphinate (LAP)” and again recites the full chemical name for LAP in lines 2-3 (i.e. “lithium phenyl-2,4,6-trimethylbenzoylpho-sphinate”). Appropriate correction is required.
Claim 9 is objected to because of the following informalities: Claim 9 depends from withdrawn claim 8. Applicant should amend the claim to incorporate the limitation of claim 8 into claim 9 and delete the dependency. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 1-7 and 9 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 pre-AIA the applicant regards as the invention.
Claim 1 recites “(5) mixing the HA-Glu/Col mixed solution prepared in step (1), the GelMA solution prepared in step (3) and the NaCMC solution prepared in step (4), respectively,” where it is unclear what “respectively” means in the context of the claim because it is unclear if Applicant means to limit the mixing order or not because there are no respective elements as for example in claim 2, lines 7-10. Appropriate clarification is required. Claims 2-7 and 9 depend from and inherit the same above discussed issue, and are therefore rejected for the same.
Claims 2-3 and 9 each recite “preferably” (claim 2, line 7; claim 3, line 6; and claim 9 lines 5, 7 & 10) which renders those claims indefinite. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
In the present instance, claim 2 recites the broad recitation generic mass volume concentration of hyaluronic acid, EDC, NHS and L-glutamic acid HCl the claim also recites the mass volume concentration of hyaluronic acid, EDC, NHS and L-glutamic acid HCl are 1%, 0.72%, 0.44% and 1.46%, respectively which is the narrower statement of the range/limitation.
In the present instance, claim 3 recites the broad recitation a “total mass volume concentration of the hyaluronic acid-glutamic acid polymer to the collagen as a solute in the solution” is generic, and the claim also recites “preferably, a total mass volume concentration of the hyaluronic acid-glutamic acid polymer to the collagen as a solute in the solution is 2%, and a mass ratio of the hyaluronic acid-glutamic acid polymer to the collagen is 1:7-7:1, more preferably, 1:1” which is the narrower statement of the range/limitation.
In the present instance, claim 9 recites the broad recitation “performing light-cured 3D printing […] to obtain the composite hydrogel scaffold”, and the claim also recites “preferably, in a light-cured 3D printer, a deposition platform is at a temperature of 29°C, and a material tank is at a temperature of 29°C;” which is the narrower statement of the range/limitation. Claim 9 further recites the broad recitation a layer thickness, light intensity, an exposure time of basic layers, and an exposure time of sheet layers are generic, and the claim also recites “preferably, a single-layer thickness is 100 µm, a light intensity is 15 mW/cm², a number of basic layers is 5, an exposure time of basic layers is 20s, and an exposure time of sheet layers is 20s;” which is the narrower statement of the range/limitation. Claim 9 further recites the broad recitation a Z-axis speed, a stripping distance, a stripping speed, and a stripping recovery speed are generic, and the claim also recites “preferably, a Z-axis speed is 25 mm/min, a stripping distance is 6 mm, a stripping speed is 25 mm/min, and a stripping recovery speed is 100 mm/min.” which is the narrower statement of the range/limitation.
The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Citation of Pertinent Art
The examiner cites BAGLEY (US 2020/0179563 A1; published June, 2020) as the closest prior art teaching 3D printing inks made from natural extracellular matrix molecules which include type I collagen, hyaluronic acid and other ECM molecules ([0064], Example 6 – [0114]), and GelMA with the photoinitiator LAP ([0080] to [0082]). BAGLEY does not teach the inclusion carboxymethyl cellulose, the hyaluronic acid-glutamic acid polymer (HA-Glu), or the specific method steps claimed – A method for preparing a composite hydrogel, comprising:
(1) grafting L-glutamic acid containing an amino group to a molecular chain of hyaluronic acid containing a carboxyl group through a peptide bond to obtain a hyaluronic acid-glutamic acid polymer (HA-Glu); dissolving the hyaluronic acid-glutamic acid polymer (HA-Glu), type I collagen (Col) and sodium chloride in an HCl solution to form a mixed solution of the hyaluronic acid-glutamic acid polymer and the collagen;
(2) dissolving a photoinitiator lithium phenyl-2,4,6-trimethylbenzoylpho-sphinate (LAP) in an NaCl solution and heating a resulting solution in a water bath to form an LAP solution;
(3) dissolving gelatin methacryloyl (GelMA) in the LAP solution, and heating a resulting solution in a water bath until the gelatin methacryloyl fully dissolves to form a gelatin methacryloyl solution;
(4) dissolving sodium carboxymethyl cellulose (NaCMC) in the LAP solution, and heating a resulting solution in a water bath until the sodium carboxymethyl cellulose fully dissolves to form a sodium carboxymethyl cellulose solution; and
(5) mixing the HA-Glu/Col mixed solution prepared in step (1), the GelMA solution prepared in step (3) and the NaCMC solution prepared in step (4), respectively, then adding a tartrazine with light-blocking property, and performing sterile filtration with a 0.22 µm sterile filter to finally obtain the composite hydrogel.
Muramatsu et al. (“Characterization of poly(L-glutamic acid)-grafted hyaluronan as a novel candidate medicine and biomedical device for intra-articular injection,” 2017, WILEY; Journal of Biomedical Materials Research A, Vol 105A, Issue 11, pp. 3006-3016) teaches poly(L-glutamic acid)-graft-hyaluronic acid (PGA-g-HA produced using ECD chemistry (p. 3008, col. 1, paragraphs 2-3) for increased resistance to hydrolysis (p. 2007, col. 1, 2nd paragraph, and col. 2). The examiner further cites YASUGI (US 2013/0338352 A1; published December, 2013) teaching hyaluronic acid modified with an amino-carboxylic acid including glutamic acid (see whole document, particularly [0308]-[0309] & [0372] – Example 1-4-3). The examiner further cites PICART (US 2011/0274744 A1; published November, 2011) teaching EDC/NHS coupling chemistry ([0041] to [0059]), and particularly teaching buffer such as MES and NaCl solutions in paragraph ([0059])(instant claim 2).
HUANG (US 2024/0216581 A1 with priority to CN-202110988608.X filed 08/2021) is cited as teaching a photocurable composite hydrogel matrix precursor including GelMa compositions, where the photoinitiator (LAP) is dissolved in phosphate buffered saline (PBS) (see whole document, particularly [0007] through [0024], [0039]-[0040], and Example 1).
Benjamin et al. (“Light-based 3D printing of hydrogels with high-resolution channels,” 2019, IOP-Publishing; Biomedical Physics & Engineering Express, Vol. 5, Article 025035, pp. 1-10) is cited as teaching tartrazine as a photoblocker in 3D printed hydrogel compositions (see whole document, particularly §Background; and p. 8, col 1, 2nd paragraph).
TAMAYOL (US 2020/0123485 A1; published April, 2020) is cited as teaching bioprinter devices/system for printing soft gels (hydrogels) for the treatment of musculoskeletal and skin disorders (see whole document, particularly [0009], [0080]).
The examiner further notes that Han et al. (cited above) is consistent with the instant disclosure/claims and is considered a non-prior art publication of Applicants work (instant claim 1, step 5).
Conclusion
Claims 1-7 and 9 are pending and have been examined on the merits.
Claims 1, 2, 4 and 9 are objected to; and claims 1-7 and 9 are rejected under 35 U.S.C. 112(b).
No claims allowed at this time.
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/IVAN A GREENE/Examiner, Art Unit 1619
/SUE X LIU/Supervisory Patent Examiner, Art Unit 1616
1 “The Photoinitiator Lithium Phenyl (2,4,6-Trimethylbenzoyl) Phosphinate with Exposure to 405 nm Light Is Cytotoxic to Mammalian Cells but Not Mutagenic in Bacterial Reverse Mutation Assays,” 2020, MDPI, Polymers, Vol. 12, 1489, pp. 1-13.
2 “Cell-laden printed hydrogel scaffolds with glutamic acid-modified hyaluronic acid/collagen concentration gradients for directional neural stem cell migration,”2025, ELSEVIER, International Journal of Biological Macromolecules, Vol. 322, article 146987, pp. 1-18.