DETAILED ACTION
Applicant's submission filed on November 26, 2025 has been entered. All arguments have been fully considered. Claims 41-47 and 49-67 are currently pending. Claims 41, 44-45 and 54-55 are currently amended. Claims 1-40 and 48 are cancelled. Claims 56-67 are new.
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 .
New Ground of Rejection, Necessitated by Amendment
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 56-58 and 62-64 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 56-58 and 62-64 make reference to “the cultured meat” and “the edible cultured meat”. It is noted these limitations render the claims indefinite since it is unclear if Applicant means to recite a method step. Claims 56-58 depend directly or indirectly from 41 and claims 62-64 depend directly or indirectly from claim 44. Claims 41 and 44 are directed to a composition. Thus, it is unclear what the limitations to “the cultured meat” and “the edible cultured meat” are meant to convey in claims 56-58 and 62-64.
In the interest of compact prosecution, given claims 41 and 44 are directed to compositions, it is noted said limitations of claims 56-58 and 62-64 are interpreted as only to be directed to intended use which does not further define or limit the composition, per se. Compositions are defined by their physical, structural, and chemical properties, not by an intended use or application.
Rejection(s) Maintained/Updated
Claim(s) 41-44, 46 and 49-55, and new claims 56-58 and 62-64, are rejected under 35 U.S.C. 103 as being unpatentable over Gorfien et al., (WO 1998/008934; IDS 2/14/2024) (“Gorfien”), as evidenced by Klingler et al., (Biotechnol Bioeng. 2021;118:3015-3028; previously cited)(“Klingler”) and Reinhart et al., (Biotechnology Journal, 2019, 14, 1700686, 11 pages) (“Reinhart”).
The rejection has been updated in view of Applicant’s amendment submitted November 26, 2025. Claims 41 and 44 have been amended to now recite the limitation “…wherein the population of connective tissue cells is capable of producing cultured meat.”
Regarding claims 41 and 44, it is first noted that claims 41 and 44 are directed to compositions.
Claim 41 as currently written is interpreted as a composition comprising two components as follows:
A liquid in vitro cellular growth medium (devoid of serum); and
An enriched population of connective tissue cells (at least 70% are anchorage-independent single cells, the cells are not aggregates), and the connective tissue cells are selected from the group consisting of avian, bovine, pig, goat, sheep, and fish connective tissue cells.
Claim 44 as currently written, is interpreted as a composition comprising three components as follows:
A matrix;
A liquid in vitro cellular growth medium (devoid of serum); and
An enriched population of connective tissue cells (at least 70% are anchorage-independent single cells, the cells are not aggregates), and the connective tissue cells are selected from the group consisting of avian, bovine, pig, goat, sheep, and fish connective tissue cells.
It is noted that, Applicant’s specification discloses the matrix encompasses a collagen matrix, a dermal matrix, an inorganic matrix, a porous scaffold (e.g., polylactic acid) ([0063]), or a soy-protein matrix ([0064]), and the cells are layered on the matrix ([0065]).
Although claims 41 and 44 recite the limitation “wherein at least 70% of the connective tissue cells are anchorage-independent single cells, and are not aggregates”, it is noted this limitation is directed to the manner by which the population of connective tissue cells were prepared, i.e., adapted to anchorage-independent growth as a single-cell suspension ([0088]-[0089]). Such limitations are product-by-process limitations which appear to define the connective tissue cells. Product-by-process limitations are considered only insofar as the method of production imparts distinct structural or chemical characteristics or properties to the product. Therefore, if the product, as claimed, is the same or obvious over a product of the prior art (i.e., it is not structurally or chemically distinct), the claim is considered unpatentable over the prior art, even though the prior art product is made by a different process. In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985), and In re Garnero, 412 F.2d 276, 279, 162 USPQ 221, 223 (CCPA 1979). See also MPEP § 2113.
In the instant case, the specification discloses the population of connective tissue cells express cellular markers indicative of connective tissue, and the markers are expressed at levels comparable to levels expressed in anchorage-dependent cells of the same connective tissue. If the product by process limitations are considered, the method by which the cell population has been produced results in maintaining a comparable marker phenotype that is indicative of anchorage-dependent connective tissues cells, and wherein the cells are single cells that are dissociated from one another and therefore not forming aggregates of multiple cells.
If the product by process limitations are considered, any population of connective tissue cells having at least 70% of the cells being single cells that are dissociated and not aggregated, whether they are grown in vitro under anchorage-dependent or anchorage-independent conditions, would appear to read on the connective tissue cells provided with the matrix.
It is further noted the limitation directed to “the connective tissue cells are selected from the group consisting of avian, bovine, pig, goat, sheep, and fish connective tissue cells” is directed to the manner by which the enriched population of connective tissue cells were prepared. Such limitations are product-by-process limitations which appear to define the connective tissue cells. Product-by-process limitations are considered only insofar as the method of production imparts distinct structural or chemical characteristics or properties to the product. Therefore, if the product, as claimed, is the same or obvious over a product of the prior art (i.e., it is not structurally or chemically distinct), the claim is considered unpatentable over the prior art, even though the prior art product is made by a different process. In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985), and In re Garnero, 412 F.2d 276, 279, 162 USPQ 221, 223 (CCPA 1979). See also MPEP § 2113.
In the instant case, the method by which the connective tissue cells have been produced (isolated from various animal sources) is not sufficiently detailed so as to impart any unique structural or biochemical properties to the cells. Thus, any population of animal connective tissue cells would appear to read on the recited connective tissue cells.
Further regarding claims 41 and 44, and the amended limitation “…wherein the population of connective tissue cells is capable of producing cultured meat”, it is noted Applicant’s specification at [067] discloses that cells for cultured meat include fibroblasts, adipocytes and myoblasts, for example.
Gorfien is directed to serum-free (i.e., devoid of serum) mammalian cell culture formulations and suspension cultures using the serum-free medium (i.e., liquid in vitro cellular growth medium, medium is devoid of serum). Gorfien teaches the serum-free media is suitable for suspension culture of epithelial cells and fibroblasts cells (i.e., connective tissue cells, wherein the population of connective tissue cells is capable of producing cultured meat), wherein the fibroblasts cells are Chinese Hamster Ovary (CHO) cells (Abstract; page 1, lines 4-10; page 10, lines 5-10; Figure 5A).
Gorfien teaches fibroblasts, the same cell type as disclosed by Applicant ([067]). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Further regarding claim 44 and the inclusion of a matrix, it is noted that Gorfien teaches the culture media may include additional components, such as one or more extracellular matrix components (page 53, line 26), and Gorfien, at Cultivation of Cells (pages 59-60), teaches cultivation of the mammalian cells wherein the cells are seeded into or onto a natural or synthetic three-dimensional support matrix such as a preformed collagen gel or a synthetic biopolymeric material. Thus, Gorfien does render obvious a composition comprising connective tissue cells, a liquid cellular growth medium that is devoid of serum, and a matrix, that is, Gorfien teaches the limitations required by the current claims and as all limitations are found in one reference it is held that a composition comprising connective tissue cells, a liquid cellular growth medium that is devoid of serum and a matrix is within the scope of the teachings of Gorfien, and thus renders the invention of claim 44 prima facie obvious. The rationale to support this conclusion of obviousness is that the single reference provides the teachings and suggestion to combine connective tissue cells, a liquid cellular growth medium that is devoid of serum with a three-dimensional matrix. Furthermore, there is no evidence on the record that shows that the claimed limitation has any greater or unexpected results than that exemplified by Gorfien.
Moreover, Klingler evidences that Chinese Hamster Ovary (CHO) cells express extracellular matrix proteins, e.g., laminin, fibronectin, collagen IV (Abstract; page 3022, right col; Figure 5C).
As to claims 41 and 44 and the limitation regarding “single cells and not aggregates”, it is noted that Gorfien teaches a need remains for a defined medium that reduces cell clumping and facilitates high density growth since cell clumping, or formation of aggregates, may interfere with successful subculturing and reduce growth rates since clumping decreases the overall cellular surface area that is exposed to culture medium, thus depriving the cells of nutrition (page 12, lines 2-12).
Gorfien’s culture medium comprises an anti-clumping agent which is used in amounts sufficient to prevent cell clumping, thus unlike traditional serum-free media, Gorfien’s culture promotes cultivation of single cells in suspension since such conditions permit high-density culture which is advantageous for the production of biological products (page 41, lines 1-26).
Therefore, although Gorfien does not comment on the percentage of cells that are single-cells (not aggregated), it would have been prima facie obvious to one having ordinary skill in the art at the time of the invention to optimize the reduction in cell clumping by optimizing the amount of anti-clumping agent that is sufficient to prevent cell clumping as a matter of routine experimentation as it is a recognized result effective variable. Moreover, at the time of the claimed invention, one of ordinary skill in the art would have been motivated by routine practice to optimize the amount of single cells with a reasonable expectation for successfully increasing the overall cellular surface area that is exposed to culture medium, thus increasing the amount of nutrition to the cells and forming a high-density cell culture which is advantageous for the production of biological products; thus, meeting the limitation of claims 41 and 44.
Regarding claim 42, it is noted that Gorfien teaches the suspension culture provides for achieving a high-density of cells (page 12, lines 2-12). Gorfien teaches the term high-density refers to a cellular density ranging from about 1 x 106 to about 2 x 107 cells/ml (page 26, lines 17-19) (claimed range overlaps the prior art range). In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05
Regarding claim 43 and the limitation the culture is devoid of microcarrier beads, it is noted that Gorfien teaches the disclosed culture medium advantageously facilitates the suspension cultivation of cells without the use of microcarriers such as latex or collagen beads (page 55, lines 17-19), thus meeting the limitation of claim 43.
Regarding claim 46, Gorfien teaches a collagen matrix, thus meeting the limitation of claim 46.
Regarding claims 49-50, Gorfien teaches the suspension culture medium comprises Pluronic F-68 ((page 15, line 15, see specification [0080]), thus meeting the limitations of claims 49-50.
Regarding claim 51 and the limitation “wherein the connective tissue cells are anchorage-independent for at least 4 passages”, it is noted this limitation is directed to the manner by which the enriched population of cells were prepared, i.e., passaged at least 4 times in an anchorage-independent culture. Such limitations are product-by-process limitations which appear to define the connective tissue cells, i.e., at least passage 4 cells. Product-by-process limitations are considered only insofar as the method of production imparts distinct structural or chemical characteristics or properties to the product. Therefore, if the product, as claimed, is the same or obvious over a product of the prior art (i.e., it is not structurally or chemically distinct), the claim is considered unpatentable over the prior art, even though the prior art product is made by a different process. In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985), and In re Garnero, 412 F.2d 276, 279, 162 USPQ 221, 223 (CCPA 1979). See also MPEP § 2113.
In the instant case, the method by which the connective tissue cells have been produced (passaged at least 4 times in suspension culture) is not sufficiently detailed so as to impart any unique structural or biochemical properties to the cells. Thus, any population of animal connective tissue cells comprising at least 70% single cells that are not aggregated would appear to read on the recited connective tissue cells, regardless of passage number.
As set forth above at the rejection of claims 41 and 44, Gorfien teaches connective tissue cells, e.g., CHO cells.
Regarding claims 52-53, it is noted the recited limitations are directed to the source of the connective tissue cells, i.e., manner by which the cells are produced. Claim 52 indicates the cells are produced by a cow and claim 53 indicates the cells may be produced by chicken, duck, goose or turkeys. Such limitations are product-by-process limitations which appear to define the connective tissue cells. Product-by-process limitations are considered only insofar as the method of production imparts distinct structural or chemical characteristics or properties to the product (i.e., the cells). Therefore, if the product, as claimed, is the same or obvious over a product of the prior art (i.e., it is not structurally or chemically distinct), the claim is considered unpatentable over the prior art, even though the prior art product is made by a different process. In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985), and In re Garnero, 412 F.2d 276, 279, 162 USPQ 221, 223 (CCPA 1979). See also MPEP § 2113.
In the instant case, the method by which the connective tissue cells have been produced (isolated from various animal sources) is not sufficiently detailed so as to impart any unique structural or biochemical properties to the cells. Thus, any population of animal connective tissue cells would appear to read on the recited connective tissue cells.
Regarding claim 54, it is initially noted the limitation directed to “the cells are spontaneously immortalized”, is directed to the manner by which the enriched population of connective tissue cells were prepared ([0111]-[0112]). Such limitations are product-by-process limitations which appear to define the connective tissue cells, i.e., immortalized. Product-by-process limitations are considered only insofar as the method of production imparts distinct structural or chemical characteristics or properties to the product. Therefore, if the product, as claimed, is the same or obvious over a product of the prior art (i.e., it is not structurally or chemically distinct), the claim is considered unpatentable over the prior art, even though the prior art product is made by a different process. In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985), and In re Garnero, 412 F.2d 276, 279, 162 USPQ 221, 223 (CCPA 1979). See also MPEP § 2113.
In the instant case, if the product by process limitations are considered, any population of immortalized connective tissue cells, whether they are spontaneously immortalized via natural processes (e.g., cancer cell) or they are immortalized via genetic modification to express telomerase via hTERT, would appear to read on the connective tissue cells provided with the matrix.
Gorfien teaches using CHO (Chinese hamster ovary) cells, specifically CHO-K1 and CHO DG44 cells (page 64, lines 19-26). Reinhart evidences that Chinese hamster ovary cells, and various lineages, e.g., CHO-K1 or CHO-DG44, were generated by Dr. Theodore Puck in 1956 from a spontaneously immortalized culture of ovarian cells (Introduction, page 1 of 11). Thus, Gorfien teaches immortalized connective tissue cells, thus meeting the limitation of claim 54.
Regarding claim 55, it is noted that Gorfien teaches the cells may be primary cells or normal cells, as compared to diseased or genetically altered cells (page 54, lines 8-11), thus meeting the limitation of claim 55.
Regarding claims 56-58 and 62-64 and the limitations directed to “the cultured meat” and “the edible cultured meat”, it is first noted that Gorfien teaches fibroblasts, such as Chinese Hamster Ovary (CHO) cells (Abstract; page 1, lines 4-10; page 10, lines 5-10; Figure 5A).
It is further noted, as set forth above at the Rejection under 35 USC 112(b), the limitations directed to “the cultured meat” and “the edible cultured meat” are interpreted as only to be directed to intended use which does not further define or limit the composition, per se. Compositions are defined by their physical, structural, and chemical properties, not by an intended use or application. As such, claims 56-58 and 62-64 do not further limit parent claims 41 and 44, and thus claims 56-58 are included in the rejection of claim 41 and claims 62-64 are included in the rejection of claim 44.
Claim(s) 41-44, 46, 49 and 51-55, and new claims 56-58 and 62-64, are rejected under 35 U.S.C. 103 as being unpatentable over Smith et al., (WO 2000/046354; see PTO-892) (“Smith”), as evidenced by Klingler (set forth above, previously cited) and Reinhart (set forth above).
The rejection has been updated in view of Applicant’s amendment submitted November 26, 2025. Claims 41 and 44 have been amended to now recite the limitation “…wherein the population of connective tissue cells is capable of producing cultured meat.”
As set forth above regarding claims 41 and 44, it is noted that claims 41 and 44 are directed to compositions.
Claim 41 as currently written is interpreted as a composition comprising two components as follows:
A liquid in vitro cellular growth medium (devoid of serum); and
An enriched population of connective tissue cells (at least 70% are anchorage-independent single cells, the cells are not aggregates), and the connective tissue cells are selected from the group consisting of avian, bovine, pig, goat, sheep, and fish connective tissue cells.
Claim 44 as currently written, is interpreted as a composition comprising three components as follows:
A matrix;
2)A liquid in vitro cellular growth medium (devoid of serum); and
An enriched population of connective tissue cells (at least 70% are anchorage-independent single cells, the cells are not aggregates), and the connective tissue cells are selected from the group consisting of avian, bovine, pig, goat, sheep, and fish connective tissue cells.
It is noted that, Applicant’s specification discloses the matrix encompasses a collagen matrix, a dermal matrix, an inorganic matrix, a porous scaffold (e.g., polylactic acid) ([0063]), or a soy-protein matrix ([0064]), and the cells are layered on the matrix ([0065]).
Although claims 41 and 44 recite the limitation “wherein at least 70% of the connective tissue cells are anchorage-independent single cells, wherein the cells are not aggregates”, it is noted this limitation is directed to the manner by which the enriched population of connective tissue cells were prepared, i.e., adapted to anchorage-independent growth as a single-cell suspension ([0088]-[0089]). Such limitations are product-by-process limitations which appear to define the connective tissue cells. Product-by-process limitations are considered only insofar as the method of production imparts distinct structural or chemical characteristics or properties to the product. Therefore, if the product, as claimed, is the same or obvious over a product of the prior art (i.e., it is not structurally or chemically distinct), the claim is considered unpatentable over the prior art, even though the prior art product is made by a different process. In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985), and In re Garnero, 412 F.2d 276, 279, 162 USPQ 221, 223 (CCPA 1979). See also MPEP § 2113.
In the instant case, the specification discloses the population of connective tissue cells express cellular markers indicative of connective tissue, and the markers are expressed at levels comparable to levels expressed in anchorage-dependent cells of the same connective tissue. If the product by process limitations are considered, the method by which the cell population has been produced results in maintaining a comparable marker phenotype that is indicative of anchorage-dependent connective tissues cells, and wherein the cells are single cells that are dissociated from one another and therefore not forming aggregates of multiple cells.
If the product by process limitations are considered, any population of connective tissue cells having at least 70% of the cells being single cells that are dissociated and not aggregated, whether they are grown in vitro under anchorage-dependent or anchorage-independent conditions, would appear to read on the connective tissue cells provided with the matrix.
It is further noted the limitation directed to “the connective tissue cells are selected from the group consisting of avian, bovine, pig, goat, sheep, and fish connective tissue cells” is directed to the manner by which the enriched population of connective tissue cells were prepared. Such limitations are product-by-process limitations which appear to define the connective tissue cells. Product-by-process limitations are considered only insofar as the method of production imparts distinct structural or chemical characteristics or properties to the product. Therefore, if the product, as claimed, is the same or obvious over a product of the prior art (i.e., it is not structurally or chemically distinct), the claim is considered unpatentable over the prior art, even though the prior art product is made by a different process. In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985), and In re Garnero, 412 F.2d 276, 279, 162 USPQ 221, 223 (CCPA 1979). See also MPEP § 2113.
In the instant case, the method by which the connective tissue cells have been produced (isolated from various animal sources) is not sufficiently detailed so as to impart any unique structural or biochemical properties to the cells. Thus, any population of animal connective tissue cells would appear to read on the recited connective tissue cells.
Further regarding claims 41 and 44 and the amended limitation “…wherein the population of connective tissue cells is capable of producing cultured meat”, it is noted Applicant’s specification at [0067] discloses that cells for cultured meat include fibroblasts, adipocytes and myoblasts, for example.
Smith is directed to apparatus and processes for the growth of cells (e.g., insect cells, or cells used in expression systems) to high density (Abstract; page 11, lines 9-10; page 12, lines 15-20). Smith teaches the apparatus circulates cells through the hollow fiber filter thus disrupting clumped cell since clumped cells are not as efficient in producing cell products since the cells on the interior of the clumps cannot easily absorb nutrients and oxygen, nor can they easily eliminate waste products, as compared to the outer cells (page 11, lines 31-33 to page 12, lines 1-2). Smith teaches the high-density culture grows the cells continuously as single cell suspension (i.e., cells are not aggregates) in a commercial serum-free medium (i.e., in vitro growth medium devoid of serum) (page 13, lines 4-8).
Smith, at Example 5, specifically teaches the culture composition having a lack of cell aggregation and cultures were grown to high-densities ranging from 74.6 x 106 and 93.4 x 106 cells/ml, wherein less than 1.5% of the cells were aggregated in the high-density cultures (i.e., wherein at least 70% of the connective tissue cells are anchorage-independent single cells, wherein the cells are not aggregates).
Although Example 5 of Smith differs from the instant invention in that Example 5 exemplifies Sf900+ insect cells, it is noted that Smith further teaches the process provides beneficial conditions for many cell types including vertebrate cells such as fish cells (e.g., shark, salmon, rainbow trout) or mammalian cells (e.g., Chinese hamster ovary (CHO) cell lines (connective tissue cells, “…wherein the population of connective tissue cells is capable of producing cultured meat”), NIH3T3 cells (mouse fibroblasts, connective tissue cells, “…wherein the population of connective tissue cells is capable of producing cultured meat”), or avian cells (e.g., chicken, turkey, duck) (page 21, lines 31-33 to page 22, lines 1-11 and 25-28).
Smith teaches fibroblasts, the same cell type as disclosed by Applicant ([067]). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Thus, Smith does render obvious a composition comprising connective tissue cells and a liquid in vitro cellular growth medium wherein the growth medium is devoid of serum, that is, Smith teaches the limitations required by the current claims and as all limitations are found in one reference it is held that a composition comprising connective tissue cells and a liquid in vitro cellular growth medium wherein the growth medium is devoid of serum is within the scope of the teachings of Smith, and thus renders the invention of claim 41 prima facie obvious. The rationale to support this conclusion of obviousness is that the single reference provides the teachings and suggestion to employ connective tissue cells. Furthermore, there is no evidence on the record that shows that the claimed limitation has any greater or unexpected results than that exemplified by Smith.
Regarding claim 42, Smith (Example 5) teaches high-density cultures ranging from 74.6 x 106 and 93.4 x 106 cells/ml (claimed range overlaps the prior art range). In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05
Regarding claim 43, Smith’s Example 5 does not employ microcarriers and Smith further teaches avoiding microcarriers since they can limit nutrient and oxygen availability and further expose the cells to unwanted sheer forces (page 6, lines 2-5). Thus, Smith does render obvious the cell composition devoid of microcarriers, that is, Smith teaches the limitation required by the current claim and as this limitation is found in one reference it is held that a composition comprising connective tissue cells and a liquid in vitro cellular growth medium wherein the culture is devoid of microcarriers is within the scope of the teachings of Smith, and thus renders the invention of claim 43 prima facie obvious. The rationale to support this conclusion of obviousness is that the single reference provides the teachings and suggestion to avoid microcarriers. Furthermore, there is no evidence on the record that shows that the claimed limitation has any greater or unexpected results than that exemplified by Smith.
Further regarding claims 44 and 46 and the inclusion of a matrix, it is noted that Smith teaches Chinese hamster ovary cells and Klingler evidences that Chinese Hamster Ovary (CHO) cells express extracellular matrix proteins, e.g., laminin, fibronectin, collagen IV (Abstract; page 3022, right col; Figure 5C).
Regarding claim 49, it is noted that Smith teaches the use of surfactant addition to the culture medium to mediate shear forces (page 6, lines 31-33 to page 7, lines 1-2), thus meeting the limitation of claim 49.
Regarding claim 51 and the limitation “wherein the connective tissue cells are anchorage-independent for at least 4 passages”, it is noted this limitation is directed to the manner by which the enriched population of cells were prepared, i.e., passaged at least 4 times in an anchorage-independent culture. Such limitations are product-by-process limitations which appear to define the connective tissue cells, i.e., at least passage 4 cells. Product-by-process limitations are considered only insofar as the method of production imparts distinct structural or chemical characteristics or properties to the product. Therefore, if the product, as claimed, is the same or obvious over a product of the prior art (i.e., it is not structurally or chemically distinct), the claim is considered unpatentable over the prior art, even though the prior art product is made by a different process. In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985), and In re Garnero, 412 F.2d 276, 279, 162 USPQ 221, 223 (CCPA 1979). See also MPEP § 2113.
In the instant case, the method by which the connective tissue cells have been produced (passaged at least 4 times in suspension culture) is not sufficiently detailed so as to impart any unique structural or biochemical properties to the cells. Thus, any population of animal connective tissue cells comprising at least 70% single cells that are not aggregated would appear to read on the recited connective tissue cells, regardless of passage number.
As set forth above at the rejection of claims 41 and 44, Smith teaches connective tissue cells, e.g., CHO cells and NIH3T3 (mouse fibroblast cells).
Regarding claims 52-53, it is noted the recited limitations are directed to the source of the connective tissue cells, i.e., manner by which the cells are produced. Claim 52 indicates the cells are produced by a cow and claim 53 indicates the cells may be produced by chicken, duck, goose or turkeys. Such limitations are product-by-process limitations which appear to define the connective tissue cells. Product-by-process limitations are considered only insofar as the method of production imparts distinct structural or chemical characteristics or properties to the product (i.e., the cells). Therefore, if the product, as claimed, is the same or obvious over a product of the prior art (i.e., it is not structurally or chemically distinct), the claim is considered unpatentable over the prior art, even though the prior art product is made by a different process. In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985), and In re Garnero, 412 F.2d 276, 279, 162 USPQ 221, 223 (CCPA 1979). See also MPEP § 2113.
In the instant case, the method by which the connective tissue cells have been produced (isolated from various animal sources) is not sufficiently detailed so as to impart any unique structural or biochemical properties to the cells. Thus, any population of animal connective tissue cells would appear to read on the recited connective tissue cells.
As set forth above at the rejection of claims 41 and 44, Smith teaches connective tissue cells, e.g., CHO cells and NIH3T3 (mouse fibroblast cells) (page 21, lines 31-33 to page 22, lines 1-11 and 25-28).
Regarding claim 54, it is initially noted the limitation directed to “the cells are spontaneously immortalized”, is directed to the manner by which the enriched population of connective tissue cells were prepared ([0111]-[0112]). Such limitations are product-by-process limitations which appear to define the connective tissue cells, i.e., immortalized. Product-by-process limitations are considered only insofar as the method of production imparts distinct structural or chemical characteristics or properties to the product. Therefore, if the product, as claimed, is the same or obvious over a product of the prior art (i.e., it is not structurally or chemically distinct), the claim is considered unpatentable over the prior art, even though the prior art product is made by a different process. In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985), and In re Garnero, 412 F.2d 276, 279, 162 USPQ 221, 223 (CCPA 1979). See also MPEP § 2113.
In the instant case, if the product by process limitations are considered, any population of immortalized connective tissue cells, whether they are spontaneously immortalized via natural processes (e.g., cancer cell) or they are immortalized via genetic modification to express telomerase via hTERT, would appear to read on the connective tissue cells provided with the matrix.
Smith teaches using CHO (Chinese hamster ovary) cells (page 21, lines 31-33 to page 22, lines 1-11 and 25-28). Reinhart evidences that Chinese hamster ovary cells were generated by Dr. Theodore Puck in 1956 from a spontaneously immortalized culture of ovarian cells (Introduction, page 1 of 11). Thus, Smith teaches immortalized connective tissue cells, thus meeting the limitation of claim 54.
Regarding claim 55 and the limitation directed to the cells are non-genetically modified cells, it is noted said limitation is directed to the manner by which the cells were produced. Such limitations are product-by-process limitations which appear to define the connective tissue cells, i.e., modified. Product-by-process limitations are considered only insofar as the method of production imparts distinct structural or chemical characteristics or properties to the product. Therefore, if the product, as claimed, is the same or obvious over a product of the prior art (i.e., it is not structurally or chemically distinct), the claim is considered unpatentable over the prior art, even though the prior art product is made by a different process. In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985), and In re Garnero, 412 F.2d 276, 279, 162 USPQ 221, 223 (CCPA 1979). See also MPEP § 2113.
In the instant case, the method by which the connective tissue cells have been produced (i.e., modified) is not sufficiently detailed so as to impart any unique structural or biochemical properties to the cells. Thus, any population of “modified” connective tissue cells, regardless of being modified non-genetically or genetically, would appear to read on the recited connective tissue cells.
Smith teaches using CHO (Chinese hamster ovary) cells (page 21, lines 31-33 to page 22, lines 1-11 and 25-28). Reinhart evidences that Chinese hamster ovary cells were generated by Dr. Theodore Puck in 1956 from a spontaneously immortalized (i.e., modified) culture of ovarian cells (Introduction, page 1 of 11). Thus, Smith teaches modified connective tissue cells, thus meeting the limitation of claim 55.
Regarding claims 56-58 and 62-64 and the limitations directed to “the cultured meat” and “the edible cultured meat”, it is first noted that Smith teaches mammalian fibroblast cells, such as NIH3T3 cells and Chinese hamster ovary (CHO) cell lines (page 21, lines 31-33 to page 22, lines 1-11 and 25-28).
It is further noted, as set forth above at the Rejection under 35 USC 112(b), the limitations directed to “the cultured meat” and “the edible cultured meat” are interpreted as only to be directed to intended use which does not further define or limit the composition, per se. Compositions are defined by their physical, structural, and chemical properties, not by an intended use or application. As such, claims 56-58 and 62-64 do not further limit parent claims 41 and 44, and thus claims 56-58 are included in the rejection of claim 41 and claims 62-64 are included in the rejection of claim 44.
Claim 50 is rejected under 35 U.S.C. 103 as being unpatentable over Smith, as evidenced by Klingler and Reinhart, as applied above to claims 41-44, 46, 49, 51-58 and 62-64, and further in view of Gorfien (set forth above).
The teaching of Smith, as evidenced by Klingler and Reinhart is set forth above.
Regarding claim 50, it is noted that, although Smith teaches the use of a surfactant to mediate shear forces, Smith does not further comment on the surfactant comprising a pluronic acid. However, Gorfien (set forth above), is directed to suspension culturing of connective tissue cells and specifically teaches employing the pluronic acid Pluronic F-68 (page 15, line 15, see specification [0080]).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time of filing the invention to substitute a pluronic acid surfactant for Smith’s disclosed surfactant since surfactants are known to mediate shear forces in suspension cultures. Therefore, one of ordinary skill in the art would recognize this as simply substituting one type of surfactant for another useful for the same purpose ((KSR Int’l Co. v. Teleflex, Inc., 550 U.S. 398 (2007) pg 14 and 12).
New Ground(s) of Rejection, Necessitated by Amendment
Claim(s) 59-60 and 65-66 are rejected under 35 U.S.C. 103 as being unpatentable over Gorfien, as evidenced by Klingler and Reinhart, as applied to claims 41-44, 46, 49-58 and 62-64 above, and as further evidenced by Mirus Bio (Maintain Suspension CHO Cells, December 18, 2023, retrieved from the internet; see PTO-892) (“Mirus Bio”) and Cellosourus CHO DG-44 (retrieved from the internet, see PTO-892).
The teaching of Gorfien, as evidenced by Klingler and Reinhart is set forth above.
Regarding claims 59-60 and 65-66, it is initially noted that Applicant’s specification at [057] discloses:
“As used herein, the term "equivalent anchorage-dependent cells" refers to the anchorage-dependent cells, who, by the methods of the invention have been converted into anchorage-independent cells. The cells are equivalent as they are the same cell type and have not been modified other than the ability to grow non-adherently has been altered.”
Gorfien does not further comment on the doubling time of the disclosed CHO-K1 and CHO DG44 cells. However, Gorfien teaches adapting the adherent CHO DG44 cells to suspension culture using the CHO-S culture medium ([0184]-[0185]) and Mirus Bio evidences that CHO cell doubling times can decrease by half (50%) for cells adapted to suspension culture. Mirus Bio notes adherent CHO cells have a doubling time of about 24 hours and Cellosaurus evidences the doubling time for CHO DG44 cells is 24.4 hours (page 1). Thus, as evidenced by Mirus Bio and Cellosaurus, Gorfient’s disclosed CHO cells would have a decreased doubling time of at least 40% in comparison to equivalent anchorage-dependent cells (claim 59 and 65) and the cells have a doubling time that is 30 hours or less (claims 60 and 66).
Claim(s) 59-60 and 65-66 are rejected under 35 U.S.C. 103 as being unpatentable over Smith, as evidenced by Klingler and Reinhart, as applied above to claims 41-44, 46, 49, 51-58 and 62-64, and as further evidenced by Mirus Bio (Maintain Suspension CHO Cells, December 18, 2023, retrieved from the internet; see PTO-892).
The teaching of Smith, as evidenced by Klingler and Reinhart is set forth above.
Regarding claims 59-60 and 65-66, it is initially noted that Applicant’s specification at [057] discloses:
“As used herein, the term "equivalent anchorage-dependent cells" refers to the anchorage-dependent cells, who, by the methods of the invention have been converted into anchorage-independent cells. The cells are equivalent as they are the same cell type and have not been modified other than the ability to grow non-adherently has been altered.”
Smith does not further comment on the doubling time of the disclosed CHO cells. However, Smith teaches adapting the cells to suspension culture (page 12, lines 18-21), and Mirus Bio evidences that CHO cell doubling times can decrease by half (50%) for cells adapted to suspension culture. Mirus Bio notes adherent CHO cells have a doubling time of about 24 hours. Thus, as evidenced by Mirus Bio, it is considered that Smith’s disclosed CHO cells would have a decreased doubling time of at least 40% in comparison to equivalent anchorage-dependent cells (claim 59 and 65) and the cells have a doubling time that is 30 hours or less (claims 60 and 66).
New Ground of Rejection, in view of Updated Search
Claim(s) 45 and 47 are rejected under 35 U.S.C. 103 as being unpatentable over Gorfien, as evidenced by Klingler and Reinhart, as applied to claims 41-44, 46, 49-58 and 62-64 above, and further in view of Elfenbein et al., (US 2020/0140821, as supported by provisional application No. 62/516,575, filed 6/7/2017; see PTO-892) (“Elfenbein”).
The teaching of Gorfien, as evidenced by Klingler and Reinhart is set forth above.
It is noted this rejection is set forth in view of an updated prior art search.
Regarding claim 45, it is noted, as set forth above regarding the rejection of claim 44, Gorfien, as evidenced by Klingler and Reinhart renders obvious a composition comprising:
a matrix;
a liquid in vitro cellular growth medium, wherein the in vitro cellular growth medium is devoid of serum; and
a population of connective tissue cells, wherein at least 70% of the connective tissue cells are anchorage-independent single cells, and are not aggregates, wherein the connective tissue cells are selected from the group consisting of avian, bovine, pig, goat, sheep, and fish connective tissue cells, and wherein the population of connective tissue cells is capable of producing cultured meat.
Gorfien teaches the culture media may include additional components, such as one or more extracellular matrix components (page 53, line 26), and Gorfien, at Cultivation of Cells (pages 59-60), teaches cultivation of the mammalian cells wherein the cells are seeded into or onto a natural or synthetic three-dimensional support matrix such as a preformed collagen gel or a synthetic biopolymeric material.
The combined prior art differs from instant claim 45 in that the combined prior art does not further teach the disclosed matrix is a vegetable-derived matrix or a plant-derived matrix.
However, Elfenbein is directed to ex vivo meat production, including sushi-grade fish meat, fish surimi, wherein the culture media includes micro-scaffolds (Abstract and [0003]) and the cultured cells include fibroblasts, myocytes, adipocytes and the cells can be obtained from fish ([0016]). Elfenbein further teaches culturing comprises growing the population of cells on a three-dimensional scaffold, e.g., micro-scaffolds within a bioreactor ([0016]), the scaffolds are typically biocompatible, such as a portion of a collagen scaffold providing support to cultured myocytes remains to provide texture and continuing structural support in the cultured food product. ([0144]). Elfenbein teaches plant-based scaffolds are used for 3D culturing, including scaffolds obtained from plants such as apples, seaweed, or jackfruit. The plant-based scaffolds often comprise at least one plant-based material such as cellulose, hemicellulose, pectin, lignin, alginate, textured vegetable protein (TVP), such as textured soy protein (TSP), which typically comprises a high percentage of soy protein, soy flour, or soy concentrate ([0144]).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time of filing the invention to substitute plant-based matrix scaffolds for the matrix scaffold disclosed by Gorfien since both are known cell culture scaffold material. Therefore, one of ordinary skill in the art would recognize this as simply substituting one type of culture matrix for another useful for the same purpose ((KSR Int’l Co. v. Teleflex, Inc., 550 U.S. 398 (2007) pg 14 and 12).
The skilled artisan would have had a reasonable expectation of success in combining the teachings of Gorfien and Elfenbein with the cited prior art because each of these teachings are directed at cell culture.
Regarding claim 47, it is noted that Elfenbein teaches the matrix scaffold includes textured soy protein (TSP), which reads on said plant-derived matrix is selected from plant which is a legume, thus meeting the limitation of claim 47.
Claim(s) 59-60 and 65-66 are rejected under 35 U.S.C. 103 as being unpatentable over Smith, as evidenced by Klingler and Reinhart, as applied above to claims 41-44, 46, 49, 51-58 and 62-64, and as further in view of Elfenbein et al., (US 2020/0140821, as supported by provisional application No. 62/516,575, filed 6/7/2017; see PTO-892) (“Elfenbein”).
The teaching of Smith, as evidenced by Klingler and Reinhart is set forth above.
It is noted this rejection is set forth in view of an updated prior art search.
Regarding claim 45, it is noted, as set forth above regarding the rejection of claim 44, Smith, as evidenced by Klingler and Reinhart renders obvious a composition comprising:
a matrix;
a liquid in vitro cellular growth medium, wherein the in vitro cellular growth medium is devoid of serum; and
a population of connective tissue cells, wherein at least 70% of the connective tissue cells are anchorage-independent single cells, and are not aggregates, wherein the connective tissue cells are selected from the group consisting of avian, bovine, pig, goat, sheep, and fish connective tissue cells, and wherein the population of connective tissue cells is capable of producing cultured meat.
It is noted that Smith teaches Chinese hamster ovary cells and Klingler evidences that Chinese Hamster Ovary (CHO) cells express extracellular matrix proteins, e.g., laminin, fibronectin, collagen IV (Abstract; page 3022, right col; Figure 5C), thus Smith’s composition comprises extracellular matrix.
The combined prior art differs from instant claim 45 in that the combined prior art does not further teach the disclosed matrix is a vegetable-derived matrix or a plant-derived matrix.
However, Elfenbein is directed to ex vivo meat production, including sushi-grade fish meat, fish surimi, wherein the culture media includes micro-scaffolds (Abstract and [0003]) and the cultured cells include fibroblasts, myocytes, adipocytes and the cells can be obtained from fish ([0016]). Elfenbein further teaches culturing comprises growing the population of cells on a three-dimensional scaffold, e.g., micro-scaffolds within a bioreactor ([0016]), the scaffolds are typically biocompatible, such as a portion of a collagen scaffold providing support to cultured myocytes remains to provide texture and continuing structural support in the cultured food product. ([0144]). Elfenbein teaches plant-based scaffolds are used for 3D culturing, including scaffolds obtained from plants such as apples, seaweed, or jackfruit. The plant-based scaffolds often comprise at least one plant-based material such as cellulose, hemicellulose, pectin, lignin, alginate, textured vegetable protein (TVP), such as textured soy protein (TSP), which typically comprises a high percentage of soy protein, soy flour, or soy concentrate ([0144]).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time of filing the invention to substitute plant-based matrix scaffolds for the matrix disclosed by Smikth since both are known cell culture matrix materials. Therefore, one of ordinary skill in the art would recognize this as simply substituting one type of culture matrix for another useful for the same purpose ((KSR Int’l Co. v. Teleflex, Inc., 550 U.S. 398 (2007) pg 14 and 12).
The skilled artisan would have had a reasonable expectation of success in combining the teachings of Smith and Elfenbein with the cited prior art because each of these teachings are directed at cell culture.
Regarding claim 47, it is noted that Elfenbein teaches the matrix scaffold includes textured soy protein (TSP), which reads on said plant-derived matrix is selected from plant which is a legume, thus meeting the limitation of claim 47.
Response to Applicant’s Remarks
Rejections under 35 USC 103:
Applicant has traversed the rejection of record on the grounds that Gorfien is not directed to producing cultured meat, as discussed at Applicant’s remarks (page 8) and the cited references to Klingler and Reinhart are not directed to producing cultured meat, as discussed at Applicant’s remarks (pages 8 and 9).
Applicant’s remarks have been carefully considered, but are not found persuasive since the claims as currently written are directed to compositions and are not directed to a method of culturing meat.
As discussed above regarding the amended limitation “…wherein the population of connective tissue cells is capable of producing cultured meat”, it is noted Applicant’s specification at [0067] discloses that cells for cultured meat include fibroblasts, adipocytes and myoblasts, for example and the cited reference to Gorfien teaches fibroblasts. Thus, it is considered that the disclosed fibroblasts are capable of producing cultured meat, absent evidence to the contrary.
Klingler and Reinhart are not relied upon for teaching “…wherein the population of connective tissue cells is capable of producing cultured meat”.
It is submitted that Klingler is relied upon to evidence that Chinese Hamster Ovary (CHO) cells express extracellular matrix proteins, e.g., laminin, fibronectin, collagen IV and Reinhart is relied upon to evidence that Chinese hamster ovary cells, and various lineages, e.g., CHO-K1 or CHO-DG44, were generated by Dr. Theodore Puck in 1956 from a spontaneously immortalized culture of ovarian cells (Introduction, page 1 of 11).
As to Applicant’s remarks that Gorfien does not comment on a specific percentage of cells that are anchorage-independent and single cells, as discussed at Applicant’s remarks (page 8), it is noted that Applicant’s remarks have been fully considered, but are not found persuasive since Gorfien teaches the inclusion of polyanionic or polycationic compounds (e.g., dextran sulfate) that inhibit cell aggregation and used in amounts sufficient to prevent cell clumping, thus unlike traditional serum-free media, Gorfien’s culture promotes cultivation of single cells in suspension since such conditions permit high-density culture which is advantageous for the production of biological products (page 41, lines 1-26).
As to Applicant’s remarks regarding the specification detailing the adaptation of the cells to an anchorage-independent growth method and rapid doubling times and sustaining a high-density, single-cell suspension growth and further culturing to produce culture meat, as discussed at Applicant’s remarks (page 10), it is noted that Applicant’s remarks have been fully considered, but are not found persuasive since the claims as currently written are directed to compositions.
Applicant has traversed the rejection of record on the grounds that Smith is not directed to producing cultured meat, as discussed at Applicant’s remarks (page 11) and the cited references to Klingler and Reinhart are not directed to producing cultured meat, as discussed at Applicant’s remarks (pages 11 and 12).
Applicant’s remarks have been carefully considered, but are not found persuasive since the claims as currently written are directed to compositions and are not directed to a method of culturing meat.
As discussed above regarding the amended limitation “…wherein the population of connective tissue cells is capable of producing cultured meat”, it is noted Applicant’s specification at [0067] discloses that cells for cultured meat include fibroblasts, adipocytes and myoblasts, for example and the cited reference to Smith renders obvious a composition comprising fibroblasts. Thus, it is considered that the disclosed fibroblasts are capable of producing cultured meat, absent evidence to the contrary.
Further as to Applicant’s remarks that the prior art CHO cells are not derived from avian, bovine, pig, goat, sheep or fish, as discussed at Remarks (pages 11-12), it is noted that Applicant’s remarks have been carefully considered, but are not found persuasive for the reasons set forth above. Specifically, that said limitation is directed to the manner by which the population of connective tissue cells were prepared. Such limitations are product-by-process limitations which appear to define the connective tissue cells and are considered only insofar as the method of production imparts distinct structural or chemical characteristics or properties to the product. Therefore, if the product, as claimed, is the same or obvious over a product of the prior art (i.e., it is not structurally or chemically distinct), the claim is considered unpatentable over the prior art, even though the prior art product is made by a different process. In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985), and In re Garnero, 412 F.2d 276, 279, 162 USPQ 221, 223 (CCPA 1979). See also MPEP § 2113.
In the instant case, the method by which the connective tissue cells have been produced (isolated from various animal sources) is not sufficiently detailed so as to impart any unique structural or biochemical properties to the cells. Thus, any population of animal connective tissue cells would appear to read on the recited connective tissue cells.
As to Applicant’s remarks regarding the rejection of claim 50, as discussed at Remarks (page 12), it is noted that Applicants rely on the arguments used in traversing the above rejection of claim 41 to also traverse this rejection without additional arguments. However, as explained above, the previous rejection stands. Therefore, the response set forth above to arguments also applies to this rejection.
Conclusion
No claim is allowed.
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E. YVONNE PYLA
Primary Examiner
Art Unit 1633
/EVELYN Y PYLA/Primary Examiner, Art Unit 1633