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 .
Claims 1-19, of record 7/7/2024, are pending and subject to prosecution.
Priority
The instant application is a national stage entry of PCT/CN2023/104613 (filed 6/30/2023). Acknowledgment is made of applicant's claim for foreign priority based on an application filed in China on 7/4/2022. It is noted, however, that applicant has not filed a certified copy of the 202210777912.4 application as required by 37 CFR 1.55.
Specification
The use of the terms Matrigel, TRIzol, Triton X-100, and AutoCAD, which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore, the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claim 19 is objected to because of the following informalities:
In line 2 of claim 19, “the removing method” should be replaced with “removing”, “removal” or the like.
Appropriate correction is required.
Claim Interpretation
Independent claim 1 recites a “microfluidic biomimetic fiber for cultured meat production”. The limitation “meat” is not defined by the instant specification. The broadest reasonable definition of “meat” is therefore considered to encompass any tissue of animal origin.
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 6-7, 9-10, and 13-14 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 6 and 9 contain the trademark/trade name Matrigel, and claim 7 contains the trademark/trade name GlutaMAX. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademarks/trade names are used to identify/describe an extracellular matrix preparation and an L-glutamine cell culture supplement and, accordingly, the identification/description is indefinite.
Claim 10 recites the limitation “same” in lines 9-10. It is unclear whether “same” is intended to refer to a stable laminar flow structure or to some other feature of the claim. Dependent claims 11-13 are included in the rejection.
Claim 13 recites the limitation “the residual collecting liquid” in line 4. There is insufficient antecedent basis for this limitation in the claim.
Claim 14 recites a use but fails to describe any active, positive steps delimiting how the use is practiced. The claim is indefinite because it attempts to claim a process without setting forth any steps involved in the process.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 14-19 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claims do not fall within at least one of the four categories of patent eligible subject matter because “use” claims that do not purport to claim a process, machine, manufacture, or composition of matter fail to comply with 35 U.S.C. 101.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2, 5, 10-12, and 14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bansai et al. (Micromachines, 2019).
Regarding claims 1, 5, 10-12, and 14: Bansai et al. teach a method for engineering skeletal muscle (which reads on “meat”) using cell-laden core-shell hydrogel microfibers formed in a double-coaxial laminar-flow microfluidic device (See Abstract and page 2, full ¶4). Murine C2C12 cells (which read on “a seed cell”, “a myoblast”, and “a muscle precursor cell”) at 1.8 × 108 cells/ml (which reads on “5×106 -5×108 seed cells/mL”) in DMEM were encapsulated in a collagen gel (which reads on “a hydrogel solution” and “an inner phase fluid”) at the center of the microfibers (See page 2, full ¶3-4 and fig. 1). The microfiber shell was formed from a sodium alginate solution (which reads on “a polymer solution with non-cell adhesion” and “an outer phase fluid”) crosslinked by a calcium chloride sheath solution under laminar flow (See fig. 1). The microfluidic device comprised glass capillary and rectangular tubes (which reads on “the microfluidic device… is made of one or more of… glass”) for extruding the nested (which reads on “coaxially nested”) solutions into a microfiber (See page 2, full ¶4 and fig. 1). The flow rate of each stream was individually adjusted, and the fabricated microfibers were cultured in a medium (which reads on “a collection medium”) to induce gelation (See page 2, full ¶4).
Regarding claim 2: Following the discussion of claims 1, 5, 10-12, and 14, Bansai et al. teach that the concentration of the sodium alginate solution was 1.5% (See page 2, full ¶4), corresponding to 15 mg/ml (which reads on “10-50 mg/mL”).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claims 1-2, 5, 10-12, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Bansai et al. (Micromachines, 2019) in view of Weymouth (Tissue Culture, 1973).
The teachings of Bansai et al. are set forward in the rejection above and are incorporated herein in their entirety.
Regarding claim 13: Following the discussion of claims 1-2, 5, 10-12, and 14, Bansai et al. teach a microfiber comprising a myoblast-laden collagen hydrogel core surrounded by an alginate shell formed by laminar flow of inner and outer phases within a calcium chloride sheath solution (which reads on “collecting liquid”) (See fig. 1). The microfiber was extruded and cultured in medium (which reads on “collection medium”) (See page 2, full ¶4). Bansai et al. do not expressly teach the washing away of residual calcium chloride solution from the microfiber prior to culturing. However, culture medium osmolarity is well-established in the art as a result-effective variable for cell survival and growth (See Weymouth, page 703, full ¶2 and page 704, full ¶1-2), and one of ordinary skill would have been motivated to wash the residual calcium chloride from the microfiber to avoid negatively impacting osmotic balance during further culturing of the cells within the microfiber.
Claims 1-3, 5-8, 10-12, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Bansai et al. (Micromachines, 2019) in view of Orban et al. (Journal of Biomedical Materials Research Part A, 2004), evidenced by Thermo Fisher (Product data sheet, 2024).
The teachings of Bansai et al. are set forth in the rejection above and are incorporated herein in their entirety.
Regarding claims 3 and 6-8: Following the discussion of claims 1-2, 5, 10-12, and 14, Bansai et al. teach a microfiber comprising a myoblast-laden collagen hydrogel core surrounded by an alginate shell but do not expressly teach the hydrogel as comprising a crosslinking agent or calcium salt-containing culture medium.
Orban et al. teach collagen gels crosslinked by transglutaminase for supporting cell growth (See Abstract). The gels comprised a 1:1 (v/v) suspension of BMSCs in DMEM and a collagen solution (which reads on “30-70% by volume of a biomaterial… and the balance of a basic culture medium”) (See page 757, col. 2, full ¶2). Transglutaminase was added at collagen:transglutaminase ratios (w/w) of 50:1, 500:1, 5000:1, or 50000:1 (See page 757, col. 2, full ¶2). Gelation occurred after 30 min incubation (See page 757, col. 2, full ¶2).
ThermoFisher teaches that DMEM comprises calcium chloride (which reads on “a calcium salt”) (See product data sheet).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the microfiber of Bansai et al. to comprise the collagen hydrogel taught by Orban et al. as the microfiber core. One would have been motivated to make this modification because Orban et al. teach that the transglutaminase-crosslinked collagen gel supports cell growth, has significantly enhanced mechanical strength, and gels in 30 min (See page 757, col. 2, full ¶2) versus 24 h for the collagen gel of Bansai et al. (See page 2, full ¶4). There would be a reasonable expectation of success in doing so because the hydrogel of Bansai et al. could be readily modified to comprise transglutaminase and a 1:1 ratio (v/v) of collagen solution to cells in DMEM.
While Orban et al. teach the relative weight rather than the volume of the transglutaminase added to the gel solution, the claimed volumes of 0.01-1% would be readily achieved through routine experimentation to optimize a wide range of collagen:transglutaminase ratios (50:1-50000:1) so that crosslinker volume would itself not significantly impact hydrogel attributes. Further, differences in properties such as volume will not support the patentability of subject matter encompassed by the prior art unless there is evidence of criticality. See MPEP 2144.05(II)(A).
Claims 1-2, 4-5, 10-12, and 14-17 are rejected under 35 U.S.C. 103 as being unpatentable over Bansai et al. (Micromachines, 2019), evidenced by Thermo Fisher (Product data sheet, 2026), in view of Li et al. (Biomaterials, 2022), of record in IDS dated 7/7/2024, and Elfenbein et al. (US 20200140821 A1).
The teachings of Bansai et al. are set forth in the rejection above and are incorporated herein in their entirety.
Regarding claims 4 and 15-17: Following the discussion of claims 1-2, 5, 10-12, and 14, Bansai et al. teach a microfiber comprising a myoblast-laden collagen hydrogel core surrounded by an alginate shell. The myoblasts underwent differentiation to myotube-like cells within the microfiber (See fig. 7). The culture medium for the myoblasts comprised DMEM (which reads on “basic culture medium”) with 10% FBS and 1% antibiotic-antimycotic (See page 2, full ¶3). The antibiotic-antimycotic reads on “penicillin-streptomycin” (See Thermo Fisher, product data sheet). Differentiation efficiency was tested using DMEM comprising 2% or 10% horse serum (which reads on “94-97% by volume of a basic culture medium, 2%-5% by volume of horse serum”) (See page 2, full ¶5). Bansai et al. do not expressly teach the inclusion of 1% antibiotic-antimycotic to the differentiation medium, however, one of ordinary skill in the art would have found it obvious to add it to the differentiation medium, like the culture medium, in order to prevent microbial contamination.
Bansai et al. do not teach the use of the microfiber in organizational integration and food processing.
Li et al. review microfluidic fabrication of cultured meat (See Abstract). Microfibers formed from microfluidic extrusion can be assembled into artificial meats with desirable internal structures (See fig. 1). Cells for cultured meats can be derived from bovine sources (which read on “cattle”) (See fig. 1 and 6). The microfibers can be woven (which reads on “organizational integration”) to fabricate muscle-like materials (See fig. 5).
Elfenbein et al. teach the production of cultured meats (See Abstract). The meat products can be processed by cooking, including frying and baking (See ¶0152). Ingredients to modulate flavor (which reads on “seasoning”) and/or texture can be incorporated into the extracellular matrix of the meat products (which reads on “pretreatment”) (See ¶0158).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Bansai et al. to comprise the use of myoblasts from animals such as cows for generating microfibers to be used in meats for human consumption. One would have been motivated to make this modification because Li et al. teach that muscle-like biomaterials can be fabricated from cell-laden microfibers (See fig. 5). There would be a reasonable expectation of success in doing so because myoblasts from other species could be used in the fiber-forming method taught by Bansai et al., and the resulting microfiber could be readily incorporated into a woven structure.
It would have been obvious to further modify the method to comprise the addition of ingredients for improving flavor and/or texture prior to cooking the cultured meat, such as is taught by Elfenbein et al. Such modifications could be readily made in order to generate an optimal product.
Claims 1-2, 4-5, 10-12, 14-17, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Bansai et al. (Micromachines, 2019), evidenced by Thermo Fisher (Product data sheet, 2026), in view of Li et al. (Biomaterials, 2022), of record, and Elfenbein et al. (US 20200140821 A1), further in view of Onoe et al. (Nature Materials, 2013), of record in IDS dated 7/7/2024.
The teachings of Bansai et al., Thermo Fisher, and Li et al. are set forth in the rejection above and are incorporated herein in their entirety.
Regarding claim 19: Following the discussion of claims 1-2, 4-5, 10-12, and 14-17, Bansai et al., evidenced by Thermo Fisher, modified by Li et al. and Elfenbein et al., render obvious the use of a microfiber comprising a myoblast-laden collagen hydrogel core surrounded by an alginate shell in food processing but do not teach removal of the shell.
Onoe et al. teach fabrication of cell-laden microfibers produced by double-coaxial laminar flow (See Abstract). The cell-containing hydrogel is surrounded by a calcium-alginate shell that is digested post-gelation with alginate lyase to leave cell fibers consisting only of cells and extracellular matrix proteins (See page 584, col. 2, full ¶1 and page 585, col. 1, ¶1).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to further modify the method rendered obvious by Bansai et al., evidenced by Thermo Fisher, modified by Li et al. and Elfenbein et al., to comprise removal of the calcium alginate shell after the hydrogel has set. One would have been motivated to make this modification because Onoe et al. teach that the digestion leaves in place a fiber consisting only of cells and extracellular matrix proteins (See page 584, col. 2, full ¶1 and page 585, col. 1, ¶1), which suggests a fiber that more closely approximates native muscle fibers. There would be a reasonable expectation of success in doing so because the microfiber in the method rendered obvious by Bansai et al., evidenced by Thermo Fisher, modified by Li et al. and Elfenbein et al., could be readily treated with an alginate lyase to remove the shell.
Allowable Subject Matter
Claim 9 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter:
Claim 9 requires a basic culture medium containing 15-25 mg/ml of the calcium salt (which can be calcium chloride, calcium carbonate, calcium sulfate, and/or calcium nitrate), which yields a calcium concentration approximately 100-fold higher than the physiological concentration of calcium in commercially available media and is not taught or suggested by the art for culturing myogenic cell lineages.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNIFER S SPENCE, whose telephone number is 571-272-8590. The examiner can normally be reached M-F 8:30-5:30.
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/JENNIFER S SPENCE/Examiner, Art Unit 1633
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