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 1-9, 12-14, and 21-28 are pending.
Claims 1-7, 12, and 14 are newly amended.
Claims 24-28 are newly added.
Claims 1-9, 12-14, and 21-28 have been examined on their merits.
Withdrawn Objections & Rejections
The objections and rejections presented herein represent the full set of objections and rejections currently pending in the application. Any objections or rejections not specifically reiterated are hereby withdrawn.
The rejection of claims 1-2, 4-7, and 11-15 under 35 U.S.C. 103 as being unpatentable over Maria Biressi et al. (WO2023139493, on IDS 12/12/2025) is withdrawn to address the claims as amended.
The rejection of claim 3 under 35 U.S.C. 103 as being unpatentable over Maria Biressi et al. (WO2023139493, on IDS 12/12/2025) as applied to claim 1 above, and further in view of Firpo et al. (WO2018208628A1, on IDS 12/12/2025) is withdrawn to address the claims as amended.
The rejection of claims 8 and 10 is rejected under 35 U.S.C. 103 as being unpatentable over Maria Biressi et al. (WO2023139493, on IDS 12/12/2025) as applied to claim 1 above, and further in view of Steurer et al. (PLOS ONE, 2018) is withdrawn to address the claims as amended.
The rejection of claim 9 under 35 U.S.C. 103 as being unpatentable over Maria Biressi et al. (WO2023139493, on IDS 12/12/2025) as applied to claim 1 above, and further in view of Kowalski et al. (US5733745A, on IDS 12/12/2025) is withdrawn to address the claims as amended.
The rejection of claim 21 under 35 U.S.C. 103 as being unpatentable over Maria Biressi et al. (WO2023139493, on IDS 12/12/2025) as applied to claim 1 above, and further in view of Elfenbein et al. (US20200140821A1, on IDS 12/12/2025) is withdrawn to address the claims as amended.
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, 4-7, 12-14, 24, and 26-28 are rejected under 35 U.S.C. 103 as being unpatentable over Maria Biressi et al. (WO2023139493, on IDS 12/12/2025, previously cited) in view of Shalgi et al. (Mol Cell, 2013) as evidenced by Siddiqui et al. (Cell Stress and Chaperones, 2020).
In regards to claim 1, Maria Biressi teaches non-human animal cell cultivation methods (specifically for culturing meat) (Claim 13; p14, lines 28-13).
In regards to step a), Maria Biressi teaches that the method comprises cultivating poultry and cattle (avian and bovine) cells with a nucleic acid sequence encoding a nucleic acid encoding a regulatory factor for myogenesis including myosin specifically and operably linked to a heat shock promoter at a proliferation temperature (claims 1-2, 13; p8, line 12-14). Since the cells proliferate, the proliferation is necessarily at a first time period. Maria Biressi also discloses that the method is carried out in a bioreactor comprising a culture medium (p17, lines 21-25; Fig. 5). Maria Biressi teaches that the bioreactor is being continuously stirred (p5, lines 29-21, referring to Fig. 5), and a person of ordinary skill in the art would have recognized that this implies that the culturing is being done in suspension. Indeed, Maria Biressi discusses culturing specific cell types in suspension (p15, lines 3-8).
In regards to step b), Maria Biressi teaches increasing the cultivation temperature to promote differentiation (thus, at a heat shock temperature to induce expression of the factor) (claim 13; Figs. 1 and 5).
In regards to steps c) and d), Maria Biressi teaches that the method includes preparing an edible product from the cultured cells (tissue) (claim 13; Figs. 1 and 5), which a person of ordinary skill in the art would have recognized requires separating the cells from the media and harvesting cells.
In regards to claim 2, Maria Biressi teaches that the cells are cultured at a proliferation temperature of 37°C (p5, line 29, Fig. 5), which overlaps with the claimed range.
In regards to claim 4, Maria Biressi teaches that the cells are exposed to a heat shock temperature of the range of 20°C and 45°C (claim 15), and specific embodiments of 37°C to 42°C (Fig. 5), which overlaps with the claimed range. A temperature of at least 42°C is at least 3°C higher than the proliferation temperature.
In regards to the timings, Maria Biressi teaches embodiments where cells are exposed to heat shock temperatures for 2 hours (Heat shock, p21, lines 18-21), which is close to a timing of at least 3 hours to about 18 hours (see MPEP 2144.05, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985)).
Furthermore, a person of ordinary skill in the art could have arrived at a timing at least 3 to about 18 hours by routine optimization, and the disclosure does not point to a criticality in this timing (see MPEP 2144.05(I)(II), 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. “[W]here 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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”).
Indeed, as taught by Shalgi mammalian cells can be heat shocked for at least 8 hours (Results, p2), which overlaps with the claimed range. Therefore, a person of ordinary skill in the art could have arrived at a timing of at least 3 to about 18 hours by routine optimization with predictable results and a reasonable expectation of success.
In regards to claims 5 and 6, Applicant should note that whether cells a substantial portion of cells express the nucleic acid after step b) at 43°C or whether 10% of the cells express the nucleic acid at or below 37°C in step a) is an inherent property of expressing a nucleic acid linked to a heat shock promoter at these temperatures. In the instant case, because Maria Biressi teaches expressing a nucleic acid linked to a heat shock promoter at the claimed temperatures, the resultant proteins would have these same properties. Furthermore, Maria Biressi also teaches that the cells increasingly express the protein over the range of 37°C to 43°C (Fig. 11, p6, line 14), and therefore, appear in fact these properties.
In regards to claim 7, similarly to as above, whether cells have a basal doubling time of about 16 to about 24 step a) and wherein the cells return to a basal doubling time within 6 days of exposure to the heat shock temperature, is an inherent property exposing cells to a heat shock promoter. Additionally, it is noted that the claims do not require a timing of 6 days exposure. In the instant case, because Maria Biressi teaches the same cells expressing the same nucleic acid linked to a heat shock promoter at the claimed temperature, the cells as taught by Maria Biressi would have this same property absent evidence to the contrary.
In regards to claim 12, Maria Biressi teaches that the step b) is carried out in a differentiation system for a second time period, comprising culturing the cells in a second bioreactor (which comprises a pipe) through which the cells flow (claim 14; Fig. 5).
In regards to claim 13, Maria Biressi is silent as to the specific timings. However, a person of ordinary skill in the art could have arrived at a timing of between 1 and 14 days by routine optimization the disclosure does not point to a criticality in this timing (see MPEP 2144.05(II)(A), 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. "[W]here 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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)). In the instant case, because in experiments prior to transfection, Maria Biressi teaches that cells can be cultured for a minimum of 3 days (Culture of porcine pericytes, p20), a person of ordinary skill in the art could have arrived at a timing of 1 to 14 days by routine optimization with predictable results and a reasonable expectation of success.
In regards to claim 14, in regards to wherein prior to step b), the cells express 1 fold to 30 fold increase in expression of factors associated with fat or muscle, Applicant should note that this is an inherent property exposing cells to any heat shock temperature for at least 3 to about 18 hours as in claim 1. Therefore, because the method of Maria Biressi as modified above carries out these steps it would result in the same fold increase as in claim 14. Moreover, because Maria Biressi teaches that cells subjected to heat shock temperatures exhibit greater than 100% increase in expression (Fig. 11), it appears that it in fact does.
Moreover, a person of ordinary skill in the art would have been motivated to increase expression of factors associated with fat or muscle in order to provide a greater number of differentiated cells prior to being formulated into a comestible food product. Furthermore, because Maria Biressi teaches that expression increases with temperature (Fig. 11) and teaches that temperature can be used to control cell type prior to being formulated into a comestible food product (Fig. 5), it could have been done with predictable results and a reasonable expectation of success.
In regards to claim 24, Maria Biressi teaches non-human animal cell cultivation methods (specifically for culturing meat) (Claim 13; p14, lines 28-13).
In regards to step a), Maria Biressi teaches that the method comprises cultivating poultry and cattle (avian and bovine) cells with a nucleic acid sequence encoding a nucleic acid encoding a regulatory factor for myogenesis or adipogenesis and operably linked to a heat shock promoter at a proliferation temperature (claims 1-2, 13; p8). Since the cells proliferate, the proliferation is necessarily at a first time period. Maria Biressi also discloses that the method is carried out in a bioreactor comprising a culture medium (p17, lines 21-25; Fig. 5). Maria Biressi teaches that the bioreactor is being continuously stirred (p5, lines 29-21, referring to Fig. 5), and a person of ordinary skill in the art would have recognized that this implies that the culturing is being done in suspension. Indeed, Maria Biressi discusses culturing specific cell types in suspension (p15, lines 3-8).
In regards to step b), Maria Biressi teaches that the cells are exposed to the HSP for 2 hours (p21, lines 18-21) which is close to a timing of at least 3 hours to about 18 hours (see MPEP 2144.05, a a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985)).
Furthermore, a person of ordinary skill in the art could have arrived at a timing at least 3 to about 18 hours by routine optimization, and the disclosure does not point to a criticality in this timing (see MPEP 2144.05(I)(II), 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. “[W]here 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.” In reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”).
Indeed, as taught by Shalgi mammalian cells can be heat shocked for at least 8 hours (Results, p2), which overlaps with the claimed range. Therefore, a person of ordinary skill in the art could have arrived at a timing of at least 3 to about 18 hours by routine optimization with predictable results and a reasonable expectation of success.
In regards to steps c) and d), Maria Biressi teaches that the method includes preparing an edible product from the cultured cells (tissue) (claim 13; Figs. 1 and 5)., which a person of ordinary skill in the art would have recognized requires separating the cells from the media and harvesting cells.
In regards to wherein cell viability in step b) (after exposing the cells to the HSP) is not reduced by more than 33% of the cell viability in step a), this is an inherent property of avian or bovine cells under control of a heat shock promoter at a temperature and for a time is sufficient to achieve this result (see paragraph [00288], “to induce expression of at least one factor or biomarker associated with fat or muscle phenotype under control of a heat shock promoter in bovine cells, the cells are cultured at a heat shock temperature . . . a temperature that activates the heat shock promoter but does not significantly . . . 33% . . . impact viability . . . for about 3 hours”; see also paragraph [0026] states, “The temperatures activate the heat shock promoter while maintaining cell viability, e.g., does not reduce cell viability by more than 1%, 5% or 10% relative to the cell viability at the culture temperature that does not activate the heat shock promoter”).
Furthermore, as evidenced by Siddiqui, mild heat stress is known to stimulate cell viability (Title, Abstract, p1033). Therefore, low reduction in cell viability (in fact, increased viability) would be the expected result.
Therefore, because Maria Biressi teaches cells under control of a heat shock promoter, and as modified, teaches culturing these cells under the claimed conditions, and because it is known in the art that heat shock conditions can promote cell viability, the method of Maria Biressi would result in reduced viability of not more than 33% as claimed absent evidence to the contrary.
In regards to claim 26, Maria Biressi teaches that the biomarker associated with a muscle phenotype can be MYOD (p11, lines 14-18). Maria Biressi also teaches that the factor associated with the fat phenotype is PPARγ (PPARG) (p12, line 2).
In regards to claim 27, Applicant should note that this is an inherent property exposing cells to any heat shock temperature for at least 3 to about 18 hours as in claim 24. Therefore, because the method of Maria Biressi as modified above carries out these steps it would result in the same fold increase as in claim 27. Moreover, because Maria Biressi teaches that cells subjected to heat shock temperatures exhibit greater than 100% increase in expression (Fig. 11), it appears that it in fact does.
Moreover, a person of ordinary skill in the art would have been motivated to increase expression of factors associated with fat or muscle in order to provide a greater number of differentiated cells prior to being formulated into a comestible food product. Furthermore, because Maria Biressi teaches that expression increases with temperature (Fig. 11) and teaches that temperature can be used to control cell type prior to being formulated into a comestible food product (Fig. 5), it could have been done with predictable results and a reasonable expectation of success.
In regards to claim 28, Maria Biressi teaches that the cells can be fibroblasts (p15, lines 21-24).
Therefore, the combined teachings of Maria Biressi and Shalgi render the invention unpatentable as claimed.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Maria Biressi et al. (WO2023139493, on IDS 12/12/2025, previously cited) in view of Shalgi et al. (Mol Cell, 2013) as applied to claim 1 above, and further in view of Firpo et al. (WO2018208628A1, on IDS 12/12/2025, previously cited).
Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over Maria Biressi et al. (WO2023139493, on IDS 12/12/2025, previously cited) in view of Shalgi et al. (Mol Cell, 2013) as evidenced by Siddiqui et al. (Cell Stress and Chaperones, 2020) as applied to claim 24 above, and further in view of Firpo et al. (WO2018208628A1, on IDS 12/12/2025, previously cited).
In regards to claims 3 and 25, Maria Biressi teaches that cells can be cultured in bioreactors with high volumes (10,000 L; p17, line 20), but is silent as to a target density.
However, as above, a person of ordinary skill in the art could have arrived at a volume of 0.1 mil/mL cells to about 70mil/mL cells by routine optimization, and the disclosure does not point to a criticality in this amount (see MPEP 2144.05(II)(A) as above).
In the instant case, because Firpo teaches that cells can be cultured to densities of a wide range about 105 cells/mL to 1010 cells/mL (paragraph [0010]) for use in formulating comestible food products (paragraph [0002]), which overlaps with the claimed ranges, a person of ordinary skill in the art could have arrived at these densities by routine optimization with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Maria Biressi, Shalgi, and Firpo renders the invention unpatentable as claimed.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Maria Biressi et al. (WO2023139493, on IDS 12/12/2025, previously cited) in view of Shalgi et al. (Mol Cell, 2013) as applied to claim 1 above, and further in view of Steurer et al. (PLOS ONE, 2018, previously cited).
In regards to claim 8, Maria Biressi teaches that the heat shock promoter can derive from the HSP70 (p9, lines 15-19) which is a family of heat shock proteins of which HSP1A1 (HSP72) is a species.
In regards to HSP1A1 specifically, a person of ordinary skill in the art would have been motivated to choose this promoter because Steurer teaches HSPA1A (HSP72) is strongly upregulated upon stress (Abstract, p1) and therefore, would be more effective for eliciting expressing of a heat shock induced response (i.e., expression of a protein driven by a heat shock promoter).
Furthermore, because Maria Biressi teaches that types of HSP70 heat shock genes can be used and because Steurer teaches that cells can be engineered to express this gene (Material and Methods, p2-3), it could have been done with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Maria Biressi, Shalgi, and Streuter renders the invention unpatentable as claimed.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Maria Biressi et al. (WO2023139493, on IDS 12/12/2025, previously cited) in view of Shalgi et al. (Mol Cell, 2013) as applied to claim 1 above, and further in view of Kowalski et al. (US5733745A, on IDS 12/12/2025).
In regards to claim 9, while Maria Biressi is silent as to whether the heat shock promoter is homologous to the species, a person of ordinary skill in the art would have been motivated to use a homologous heat shock promoter because it would be the most compatible with that species. Furthermore, because Kowalski teaches that bovines express hsp70 (column 4, lines 24-31), it could have been done with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Maria Biressi and Kowalski renders the invention unpatentable as claimed.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Maria Biressi et al. (WO2023139493, on IDS 12/12/2025, previously cited) in view of Shalgi et al. (Mol Cell, 2013) as applied to claim 1 above, and further in view of Elfenbein et al. (US20200140821A1, on IDS 12/12/2025, previously cited).
In regards to claim 21, Maria Biressi does not explicitly teach that the cells are cultivated in serum free media. However, culturing cells in serum-free conditions is long understood in the art.
A person of ordinary skill in the art would have been motivated to use serum-free conditions in order to reduce having to raise live-stock (and thus costs) in order to obtain serum and reduce contamination by viruses, mycoplasma, prions, toxins, and other undesirables present in serum as taught by Elfenbein (paragraph [0121]). Furthermore, because Elfenbein teaches that animal cells for use as in vitro meats can be grown in serum-free media (paragraph [0059]) it could have been done with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Maria Biressi, Shalgi, and Elfenbein renders the invention unpatentable as claimed.
Claim 22 is rejected under 35 U.S.C. 103 as being unpatentable over Maria Biressi et al. (WO2023139493, on IDS 12/12/2025, previously cited) in view of Shalgi et al. (Mol Cell, 2013) as applied to claim 1 above, and further in view of Chen et al. (Food Science, 12 March 2024).
In regards to claim 22, while Maria Biressi teaches that the nucleic acid can be myosin specifically (line 12-14) Maria Biressi is silent as to the specific myosin protein.
However, a person of ordinary skill in the art would have been motivated to choose MYH2 because Chen teaches that MHY2 is upregulated in fused myoblasts and that myotube formation efficiency of myoblasts in vitro is the key for simulating the structure and composition of muscle tissue in the context of cell cultured meat (Abstract, p1; The influence of groove width on the expression of fusion related genes in myoblasts, p7). Furthermore, because MYH2 is a known myosin protein gene and because Maria Biressi teaches that the nucleic acid can be myosin broadly (line 12-14), a person of ordinary skill in the art could have chosen MHY2 with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Maria Biressi, Shalgi, and Chen render the invention unpatentable as claimed.
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Maria Biressi et al. (WO2023139493, on IDS 12/12/2025, previously cited) in view of Shalgi et al. (Mol Cell, 2013) and Steurer et al. (PLOS ONE, 2018, previously cited) as applied to claims 1 and 8 above, and further in view of Corton (GenBank: FQ482128.2, 2012, retrieved from NCBI Blast 07/09/2026).
In regards to claim 23, in regards to SEQ ID NO: 29, it is noted that this sequence corresponds to the bovine HSPA1A gene. As taught by Corton this was a known sequence (GenBank: FQ482128.2; see Alignment, second page; 100% identity).
Additionally, Applicant should note that the successful cloning and sequencing of the cDNA encoding a known protein is obvious, and thus unpatentable, if (1) there was some suggestion or motivation in the prior art to clone the cDNA, and (2) there was a “reasonable expectation of success,” based on "detailed enabling methodology" in the prior art. Ex parte Kubin, 83 U.S.P.Q.2d (BNA) 1410 (B.P.A.I. 2007), aff'd, 561 F.3d 1351 (Fed. Cir. 2009).
In the instant case a person of ordinary skill in the art would have been motivated to choose this sequence because as above, Steurer teaches HSPA1A (HSP72) is strongly upregulated upon stress (Abstract, p1) and therefore, would be more effective for eliciting expressing of a heat shock induced response (i.e., expression of a protein driven by a heat shock promoter). Furthermore, because it was a sequence, and because Maria Biressi teaches that the heat shock promoter can derive from the HSP70 (p9, lines 15-19), a person of ordinary skill in the art could have chosen and cloned this sequence with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Maria Biressi, Shalgi, Steurer, and Corton render the invention unpatentable as claimed.
Response to Arguments
Applicant argues that Maria Biressi does not teach using an HSP to induce expression of myosin (Remarks, p9). Applicant argues that the instant invention drives expression of this protein directly, while Maria Biressi drives expression of regulatory factors associated with myogenesis or adipogenessis (Remarks, p10).
Applicant’s arguments filed 06/26/2026 have been fully considered but are not found persuasive.
As discussed above, Maria Biressi teaches that the regulatory factor for myogenesis includes the protein myosin specifically (p8, line 12-14).
Applicant argues that Biressi teaches adherent culture not suspension culture (Remarks, p10). In particular, Applicant argues that “continuous stirring” can apply to adherent cell culture and is not exclusive to cell culture (Remarks, p10). In particular, Applicant argues that Fig. 5 depicts scaffold within the bioreactor and a POSITA would have understood that these scaffolds serve as a structural template (Remarks, p10). Continuing, Applicant argues that even though Maria Biressi mentions suspension culture, this is in passing, and teaches the use of a heat shock promoter in an adherent cell culture (Remarks, p10).
Applicant’s arguments filed 06/26/2026 have been fully considered but are not found persuasive.
As discussed above, Maria Biressi also discloses that the method is carried out in a bioreactor comprising a culture medium (p17, lines 21-25; Fig. 5). Maria Biressi teaches that the bioreactor is being continuously stirred (p5, lines 29-21, referring to Fig. 5), and a person of ordinary skill in the art would have recognized that this implies that the culturing is being done in suspension. Indeed, Maria Biressi discusses culturing specific cell types in suspension (p15, lines 3-8).
In regards to Applicant’s arguments concerning scaffolds in in Fig. 5 as taught by Maria Biressi, in further clarification, Maria Biressi teaches that “With the purpose of conferring a pre-defined three-dimensional shape to the muscle and/or adipose tissue, in the method according to any one of the herein described embodiments, step c), that is the cell differentiation phase, can be carried out inside one or more scaffolds or three-dimensional moulds which are capable of conferring a predetermined shape to said tissue” (p18, lines 32-36).
Therefore, a person of ordinary skill in the art would have understood that the scaffold refers to a type microcarrier which is explicitly considered a type of suspension culture by the instant application (“Microcarriers are used to expand anchorage dependent cells in large-scale suspension bioreactors” paragraph [0229]). Additionally, as evidenced by Yang et al. (Cell Transplantation, 2010), “Microcarriers are widely used to expand anchorage-dependent cells in large-scale suspension bioreactors” (Introduction, p1123). Therefore, it is also well-known in the art that the use of scaffolds in bioreactors does not render the culture an “adherent culture” as argued by Applicant.
Applicant argues that Biressi Maria does not teach a heat shock exposure of at least 3 hours to about 18 hours and a minimal impact on cell viability (Remark, p10.
Applicant’s arguments filed 06/26/2026 have been fully considered but are not found persuasive.
As discussed above, in regards to the timings, Maria Biressi teaches embodiments where cells are exposed to heat shock temperatures for 2 hours (Heat shock, p21, lines 18-21), which is close to a timing of at least 3 hours to about 18 hours (see MPEP 2144.05, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985)).
Furthermore, a person of ordinary skill in the art could have arrived at a timing at least 3 to about 18 hours by routine optimization, and the disclosure does not point to a criticality in this timing (see MPEP 2144.05(I)(II), 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. “[W]here 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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”).
Indeed, as taught by Shalgi mammalian cells can be heat shocked for at least 8 hours (Results, p2), which overlaps with the claimed range. Therefore, a person of ordinary skill in the art could have arrived at a timing of at least 3 to about 18 hours by routine optimization with predictable results and a reasonable expectation of success.
In regards to wherein cell viability in step b) (after exposing the cells to the HSP) is not reduced by more than 33% of the cell viability in step a), this is an inherent property of avian or bovine cells under control of a heat shock promoter at a temperature and for a time is sufficient to achieve this result (see paragraph [00288], “to induce expression of at least one factor or biomarker associated with fat or muscle phenotype under control of a heat shock promoter in bovine cells, the cells are cultured at a heat shock temperature . . . a temperature that activates the heat shock promoter but does not significantly . . . 33% . . . impact viability . . . for about 3 hours”; see also paragraph [0026] states, “The temperatures activate the heat shock promoter while maintaining cell viability, e.g., does not reduce cell viability by more than 1%, 5% or 10% relative to the cell viability at the culture temperature that does not activate the heat shock promoter”).
Furthermore, as evidenced by Siddiqui, mild heat stress is known to stimulate cell viability (Title, Abstract, p1033). Therefore, low reduction in cell viability (in fact, increased viability) would be the expected result.
Therefore, because Maria Biressi teaches cells under control of a heat shock promoter, and as modified, teaches culturing these cells under the claimed conditions, and because it is known in the art that heat shock conditions can promote cell viability, the method of Maria Biressi would result in reduced viability of not more than 33% as claimed absent evidence to the contrary.
Applicant argues that none of Firpo, Steurer, Kowalski, or Elfenbein does not cure the deficiencies of Biressi Maria (Remarks, p11-12).
Applicant’s arguments filed 06/26/2026 have been fully considered but are not found persuasive because Biressi Maria is not deficient for the reasons discussed above.
In regards to Steurer, Applicant argues that the claimed invention is to a cultivation method comprising a heat shock promoter, not a heat shock protein or heat shock genes (Remarks, p11).
Applicant’s arguments filed 06/26/2026 have been fully considered but are not found persuasive.
As discussed above, Maria Biressi teaches that the heat shock promoter can derive from the HSP70 (p9, lines 15-19) which is a family of heat shock proteins of which HSP1A1 (HSP72) is a species.
In regards to HSP1A1 specifically, a person of ordinary skill in the art would have been motivated to choose this promoter because Steurer teaches HSPA1A (HSP72) is strongly upregulated upon stress (Abstract, p1) and therefore, would be more effective for eliciting expressing of a heat shock induced response (i.e., expression of a protein driven by a heat shock promoter).
Furthermore, because Maria Biressi teaches that types of HSP70 heat shock genes can be used and because Steurer teaches that cells can be engineered to express this gene (Material and Methods, p2-3), it could have been done with predictable results and a reasonable expectation of success
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/JOSEPH PAUL MIANO/Examiner, Art Unit 1631
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