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 .
Status of the Claims
Claims 13-16 and 19-28 are pending (claim set as filed on 05/07/2026).
Election/Restrictions
Applicant’s election without traverse of Group III in the reply filed on 05/07/2026 is acknowledged. The non-elected claims were canceled therewith.
Therefore, claims 13-16 and 19-28 are presented for examination.
Priority
This application is a 371 of PCT/CN2021/122674, which has a foreign application to CN 202110386052.7 filed on 04/09/2021.
Information Disclosure Statement
The Information Disclosure Statements (IDS) submitted on 11/07/2023 and 05/07/2026 are acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the Examiner.
Drawings
The drawings filed on 10/06/2023 have been accepted.
Claim Rejections - 35 USC §112, Indefinite
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.
Claims 13 and 19-28 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Base claim 13’s preamble recites “A method for reducing the shear damage on cells in a shear environment using a cell gel preparation” and therefore, the claimed invention, as a whole, is directed a method of use (MPEP 2111.02: Effect of the Preamble). However, the body of the claim merely recites preparation steps to assemble the nucleic acid hydrogel and therefore is rejected as being indefinite because it appears to be lacking an application step in accordance or in consonance with the preamble. The MPEP 2173.05(q) states that “Attempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness … because it merely recites a use without any active, positive steps delimiting how this use is actually practiced”. Thus, it is not clear if the claimed invention was intended to be a method of preparation instead of a method of using such that the preamble does not have a limiting scope. In other words, there is confusion as to the statutory class of invention as to whether the claimed invention is a process of use versus a process of making. Appropriate clarification is requested. Claim interpretation: for the purposes of compact prosecution and prior art examination, the preamble will be interpreted as an intended use having non-patentable weight (dependent claims 14-16 are embodiments of the intended use and also have non-limiting scope) and the claimed invention will be interpreted as a method of manufacturing/preparing a cell gel preparation.
Claim 22 recites, in part, “under physiological conditions (37°C, pH 7.2-7.4, 0.9 wt% NaCl, isotonic)” and is therefore, rejected for the use of parenthetical characters which raises confusion to whether the conditions are preferred embodiment or actual limitations. Parentheses may be used to denote an abbreviation of a term but not for examples and preferences that raises confusion as to the intended scope of the claims (MPEP 2173.05(d)).
Claims 19-21 and 23-28 are rejected because they are dependent claims that do not overcome the deficiencies of the rejected claim from which they depend.
Claim Rejections - 35 USC §103, Obviousness
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 non-obviousness.
Claims 13-16 and 19-28 are rejected under 35 U.S.C. 103 as being unpatentable over Liu (CN 109554331 A - cited by the ISA and in the IDS filed on 11/07/2023, machine translation provided) in view of Hanna (US 2016/0256604 A1).
Liu’s general disclosure is directed to “a hydrogel and its preparation method and use. The hydrogel comprises: a scaffold unit comprising a scaffold core and at least three single-stranded L-nucleic acids bound to the scaffold core, each single-stranded L-nucleic acid having at least one scaffold sticky end; a cross-linking unit, the cross-linking unit comprises a cross-linked core and at least two single-stranded L-nucleic acids combined with the cross-linked core, each single-stranded L-nucleic acid has at least one cross-linked sticky end; and an aqueous medium; the scaffold unit the crosslinking unit is cross-linked with the cross-linking sticky ends in the form of base complementary pairing through the scaffold sticky ends, thereby forming a three-dimensional spatial network structure” (see abstract & page 2: Summary of the Invention). Liu teaches “the methods for preparing nucleic acid hydrogel of the invention, to water of the invention the preparation method of gel is not particularly limited, such as can prepare the carrier unit, the crosslink unit and described respectively then aqueous medium mixes three, obtain hydrogel of the invention it can also be respectively by the carrier unit and crosslink unit the aqueous medium solution of carrier unit and the aqueous medium solution of crosslink unit are mixed to get with the aqueous medium, then by two kind solution mixing makes it be cross-linked to form three-dimensional space network structure, obtains hydrogel of the invention” (see pages 5-6: Method for preparing hydrogel of the invention). Liu teaches the hydrogel composition is in the form of a pharmaceutical sustained release and may include stem cells (see page 6: the purpose of hydrogel of the invention).
Regarding claims 19-20 pertaining to the base pair, Liu teaches the carrier unit includes bracket core and at least three single-stranded in conjunction with the bracket core nucleic acid, each single-stranded nucleic acid have at least one bracket cohesive end. There is complementary pairing area as the nucleic acid of bracket core, this is mutually recruited it can be 4-150bp (see page 5: 2nd & 3rd ¶).
Regarding claim 21 pertaining to the molar ratios, Liu teaches the carrier unit with crosslink unit is mixed under conditions o with different molar ratios (2:1, 1:1, 1:1.5, 1:2 and 1:3) (see page 7).
Regarding claim 22 pertaining to the physiological conditions, Liu teaches “the carrier unit and the crosslink unit by the bracket cohesive end with it is described cross-linked adhesive end is crosslinked in a manner of base pair complementarity, to form three-dimensional space network structure. Preferably, the bracket unit, the crosslink unit and the three-dimensional space network structure in physiological conditions (37°C, pH 7.2-7.4, 0.9 wt% NaCl, isotonic) it is in stable cross-linked state” (see page 5: middle page).
Regarding claims 23-24 pertaining to the modulus and sequence, Liu teaches the hydrogel has a mechanical strength above 0.1 Pa, ideal stability, and the carrier unit or the cross-link may include CpG sequence (see page 5). Liu teaches frequency sweep test, strain = 1% from 0.05 to 300 rad/s (see page 7).
However, Liu does not teach: loaded with mesenchymal stem cells (claim 13’s limitation); or further comprising an anti-inflammatory agent (claim 27).
Hanna’s general disclosure relates to “covalently crosslinked polymer hydrogels. Provided covalently crosslinked hydrogels are useful, for example, for cell growth applications including cell engineering and/or tissue regeneration. The present invention also provides methods of preparing and using such hydrogels” (see ¶ [0004]-[0005]).
Hanna teaches the covalently crosslinked hydrogels are characterized by mechanical properties that support living cells including human mesenchymal stem cells (see ¶ [0005], [0074], [0316]). Hydrogels are elastic and able to withstand strain or greater shear (see ¶ [0122]-[0123]). Hanna teaches “For biomedical applications, one of the material formats that can be used is a hydrogel, which allows for ease of cell infiltration, high water contents, swellability, and/or the ability to control the release of drugs and other therapeutic agents dispersed therein” (see ¶ [0119], [0150]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to employ or use mesenchymal stem cells such as taught by Hanna in the method of Liu. The ordinary artisan would have been motivated to do so is because Liu suggest stem cell in the hydrogel and Hanna more specifically teaches mesenchymal stem cells. Thus, it would be considered to be a simple substitution of one known element for another to obtain predictable results (MPEP 2141(III): Examples of Rationales that may support a conclusion of obviousness). The ordinary artisan would have had a reasonable expectation of success because both references are directed to the use of stem cell protected in a hydrogel.
Regarding claim 25 pertaining to MSCs dispersed in a hydrogel, Hanna teaches “For biomedical applications, one of the material formats that can be used is a hydrogel, which allows for ease of cell infiltration, high water contents, swellability, and/or the ability to control the release of drugs and other therapeutic agents dispersed therein” (see ¶ [0119], [0150]). Thus, it would have been obvious to dispersed MSCs in a hydrogel to protect and improve viability.
Regarding claims 26 and 28 pertaining to the density and nucleic acid content, Hanna teaches the seeding of mesenchymal stem cells at 210 cells per mm2, the cells were encapsulated (see ¶ [0316]). Liu teaches various nucleic acid content (see Liu at page 8). The MPEP 2144.05(II)(A) states that “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. 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”. Thus, the density of MSCs and nucleic acid content are parameters within the purview of the ordinary artisan to optimized dependent upon the intended application of the cell gel hydrogel preparation.
Regarding claim 27, Hanna teaches the hydrogel may contain additives or therapeutic agents including cells, proteins, peptides, nucleic acid analogues, nucleotides, oligonucleotides, nucleic acids (DNA, RNA, siRNA), peptide nucleic acids, steroids, anti-inflammatory agents, steroidal agents (see ¶ [0236]). Thus, it would be obvious from the guidance of the cited references to include or use an anti-inflammatory agent in the hydrogel dependent upon the intended application of the hydrogel.
Conclusion
No claims were allowed.
Correspondence Information
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/NGHI V NGUYEN/Primary Examiner, Art Unit 1653
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