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 .
Election/Restrictions
Applicant’s election without traverse of Inventive Group I in the reply filed on 12/30/2025 is acknowledged.
Claims 13-24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventive group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/30/2025.
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.
Claims 1-5 and 7-11 are rejected under 35 U.S.C. 103 as being unpatentable over Elfenbein et al. (WO 2020/123876 A1) in view of Glass et al. (A Synthetic Bacterial Cell-Cell Adhesion Toolbox for Programming Multicellular Morphologies and Patterns, (2018)
Regarding claim 1: Elfenbein teaches methods of producing cultured fish meat for human consumption. (0011) The culture process may include transdifferentiating the population of cells into hepatocytes, myocytes, and adipocytes (020) and further teaches use of bioreactor culture (021) and use of suspension culture. (022) This reads on the growing of multiple cell types in free suspension culture in a bioreactor. In addition to this, Elfenbein teaches that the cultured product may comprise a layer of fibers intended to align myocytes and adipocytes to mimic the alignment of muscle fibers and fat bands within a tissue. (047) This reads on assembling said cells into a desired macroscopic structure. Elfenbein fails to teach use of the docking of donor/receptor pairs for the assembly of said macroscopic structure.
Glass teaches a genetically encoded synthetic platform to direct cell to cell adhesion which allows for morphologies and patterns to be formed from the cells depending on what adhesion molecule is engineered onto the cell surface. (Pg 649, Summary) Glass further teaches that the molecular docking toolkit may be used on eukaryotic cells (Pg 656, Discussion) and this toolkit of adhesion molecules allows for the controlled organization of the cell population into various configurations such as layering, fibrous, porous, spheroid, or phase separation. (Pg 650, Results)
It would have been obvious to a person of ordinary skill in the art before the filing date of the claimed invention to combine the molecular docking toolkit taught by Glass with the cultured food product taught by Elfenbein to create a cultured food product wherein the cell types are coupled by docking donor/receptor pairs. One skilled in the art would have had motivation and a reasonable expectation of success based on the teachings of Glass, who state that use of the toolkit of surface-bound nanobodies and antigens allows for the precise manipulation of cell to cell adhesion and design of varied self-assembled patterns and morphologies (pg 648, In Brief) and that the toolkit is suitable for use in eukaryotic cells.
Regarding claims 2-4: Elfenbein fails to teach use of engineering complementary donor/receptor pairs on the cells themselves.
Glass teaches the development of a genetically encoded toolkit of surface-bound antigens and nanobodies in E. coli which allows for precise manipulation of cell to cell adhesion and allows for the formation of complex and organized structures. (Pg 650, Summary) Glass further teaches that due to multicellular organisms displaying a variety of three-dimensional morphology, interest in synthetic biology is growing. (Pg 649, Introduction) Glass makes use of three elements in the toolkit: a transcriptional regulator, outer membrane anchor, and an adhesion library. (Pg 649-650, Results) Importantly, Glass states that this docking/receptor system may be used on eukaryotic cells when suitable surface display anchors are used. (Pg 656, Discussion) This toolkit allowed for the macroscopic organization in both orthogonal and composable compositions (Pg 650, Results) which allows for various organizational structures to be created as shown in the graphical abstract below:
PNG
media_image1.png
438
412
media_image1.png
Greyscale
Use of this toolkit would allow a person of ordinary skill in the art to arrange, in theory, multiple types of cells into whatever structure is needed for the macroscopic structure and therefore when used in combination with the multicellular cultured food product taught by Elfenbein would allow for the first and second type of cells to dock together (claim 2), the first type to bind to the second type and the third type to bond to the second type (claim 3), and the first cell type to bind to the second cell type and second cell type to bind to other cells of the second type (claim 4).
Regarding claim 5: Following the discussion of claims 2-4 above, Glass teaches use of two methods for controlling the configuration of cells: control of the affinity on a per-cell basis via controlling the adhesion construct expression level and controlling affinity on a per-molecule basis by individual Nb-Ag affinity. (Pg 653, Results) This reads on use of an engineered protein binding pair.
Regarding claim 7: Elfenbein teaches the culture of cells on micro-scaffolds within a bioreactor wherein the micro-scaffolds enable cell adhesion (023) and that scaffolds may have specific shapes or sizes for guiding the growth of cultured cells. (0167) In addition to this, Elfenbein teaches use of microRNA (hereafter “miRNA”) embedded within the scaffold to modulate proliferation and differentiation of said cells. (0134) Elfenbein further teaches the culture of multiple cell types (00200 at once. While this reads on the modification of the scaffold to comprise a protein intended for binding interactions with a cell type, Elfenbein fails to teach use of engineering of the cells themselves to express a donor/receptor pair.
As discussed in the rejections of claims 2-4 and 5, incorporation of the toolkit taught by Glass would allow a person skilled in the art to engineer the first cell type to bind with the scaffold through engineered protein binding. This reads on the scaffold and first cell type binding via donor/receptor pairs.
It would be obvious to a person of ordinary skill in the art before the filing date of the claimed invention to combine the teachings of Glass to the cultured food product taught by Elfenbein to create an organized, structured cellular construct in the binding patterns specified in claims 2-4. A person of ordinary skill in the art would have motivation due to the teachings of Glass, who state that use of the claimed toolkit allows for the targeted assembly of cells into complex shapes and patterns and that the toolkit may be adapted to use in eukaryotic cells.
Regarding claims 8 and 9: Elfenbein teaches use of multiple scaffold types, including use of gelatin (claim 8) and elastin (claim 9). (009)
Regarding claim 10: Elfenbein teaches use of a scaffold modified with embedded miRNA to encourage cell attachment and differentiation as discussed above, but fails to teach use of docking donor/receptor pairs of multiple types within the same cell type, allowing the first cell type to bind both to the scaffold and the second cell type.
Glass teaches that the design of the toolkit is comprised of 8 antigens and 52 corresponding nanobodies which target said antigens, and that most of the antigens in the kit have affinities for multiple nanobodies. (Pg 650, Results) Glass further teaches that multiple adhesions can function simultaneously within one cell (pg 650, Results), allowing for one cell to bind to multiple other cell types (or substrate types) as shown in the figure below:
PNG
media_image2.png
262
236
media_image2.png
Greyscale
It would be obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the teaching of multiple binding affinities in a single cell taught by Glass with the cultured food product taught by Elfenbein to create a construct in which the first cell type binds both to the scaffold and to the second cell type. A person skilled in the art would have had motivation and a reasonable expectation of success based on the teachings of Glass, who state successful use of multiple adhesins within a single cell.
Regarding claim 11: Elfenbein fails to teach use of inducible binding of donor/receptor pairs.
Glass teaches use of TetR or AraC repressors inducible via anhydrotetracycline (hereafter “ATc”) as a regulator switch for the activation of the adhesins. (Pg 650, Results) It was shown that cells engineered with adhesins and nanobodies did not aggregate without the induction by ATc (Pg 650, Results), reading on making the assembly of the macroscopic structure via donor/receptor binding controllable. This reads on use of a shifting culture condition (here the addition of ATc) triggering the binding of donor/receptor pairs.
It would have been obvious to a person of ordinary skill in the art to combine the teaching of Glass of a TetR or AraC switch induced via ATc with the cultured food construct taught by Elfenbein to create an inducible assembly system for the cells in culture. One skilled in the art would have motivation and a reasonable expectation of success due to the teachings of Glass, who demonstrate that the arrangement of cells controlled by the adhesins and nanobodies will not occur unless the ATc induced switch is activated, allowing for control of the timing of organization of the macroscopic structure.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Elfenbein et al. (WO 2020/123876 A1) in view of Glass et al. (A Synthetic Bacterial Cell-Cell Adhesion Toolbox for Programming Multicellular Morphologies and Patterns, (2018), and Braiman et al. (The role of Crk adaptor proteins in T-cell adhesion and migration, 2015)
The teachings of Elfenbein and Glass are discussed above. Both fail to teach use of an adaptor with at least two donor or receptor binding sites.
Regarding claim 6: Braiman teaches that adaptor proteins are essential components of signal transduction pathways in all cell types because they have the ability to link engaged receptors to specific downstream signaling cascades. (Pg 1, Introduction) In addition to this, Braiman teaches that adaptor proteins comprising multiple protein-protein interaction domains enables the simultaneous interactions with two or more effector molecules at once and allows for complex signal transduction. (Pg 1, Introduction)
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the teachings of Braiman of use of adaptor proteins with multiple binding sites to the cultured food product taught by Elfenbein. A person skilled in the art would have had motivation and a reasonable expectation of success due to Braiman teaching that adaptor proteins, specifically ones with multiple protein-protein interaction domains, enables simultaneous multiple interactions with different effector molecules at once, allowing for complex signal transduction.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Elfenbein et al. (WO 2020/123876 A1) in view of Glass et al. (A Synthetic Bacterial Cell-Cell Adhesion Toolbox for Programming Multicellular Morphologies and Patterns, (2018), and Bogen et al., (Dual Function pH Responsive Bispecific Antibodies for Tumor Targeting and Antigen Depletion in Plasma, 2019)
The teachings of Elfenbein and Glass are discussed above. Both fail to teach use of either pH, temperature, or osmolarity as the shift in culture conditions.
Regarding claim 12: Bogen teaches that antibodies with pH-responsive binding modalities are able to undergo a permanent recycling process due to controlled response to pH, thereby extending the half-life of the antigen in vivo (and, by extension, in vitro) (Pg 2, Introduction)
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the teachings of Bogen of culture conditions triggered by pH shifting for use in the production of cultured food product taught by Elfenbein. One skilled in the art would have had motivation and a reasonable expectation of success at doing so based on the teachings of Bogen, who state that use of a pH shifting method allows the antibodies to be recycled and also prolongs the life of the antigen.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HANNA M THUESON whose telephone number is (571) 272-3680. The examiner can normally be reached M-F 7:30-5 EST. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Tracy Vivlemore, can be reached on (571) 272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/HANNA MARIE THUESON/ Examiner, Art Unit 1638
/Tracy Vivlemore/ Supervisory Primary Examiner, Art Unit 1638