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 .
Priority
Acknowledgement is made that the instant application is a National Stage of International application No. PCT/EP2022/057221 (filed 03/18/2022). Additionally, the application claims priority to French application number FR2102786 (filed 03/19/2021).
Claim Interpretation
Claim 1 requires the limitation “cells requiring a supply of ferric iron”. Hentze (Cell, 2004) teaches all Eukaryotic cells require iron for survival and proliferation (See Sec. The Dual Challenge). Hentze further teaches ferric iron bound to transferrin enters cells through ubiquitously expressed TfR1 receptors in most cell types (See Sec. Cellular Iron Uptake). Therefore, “cells requiring a supply of ferric iron” is being interpreted as any eukaryotic cell.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-3, 5-7, 11, and 13-14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nahmias (US20200080050A1) as evidenced by Millipore Sigma (M199 Formulation).
Nahmias discloses a method of for growing cells in a circulating perfusion bioreactor comprising system to deliver a perfusion solution to the bioreactor chamber and a dialysis system having a filter for filtering the perfusion solution as it exits the bioreactor and re-circulates through the bioreactor (See claims 1-2 and Figs. 2 and 9). The dialyzer comprises a filter having a molecular weight cut-off of 30 kDa in a preferred embodiment (See ¶0306) and can be a hollow fiber dialyzer (See ¶0170 and 0609). In other embodiments, the dialyzer has a cut-off ranging from 10-60 kDa (See ¶0285). The method of Nahmias can be used to culture cells that form a cultured meat product (See claim 8). In some embodiments, the method comprises culturing immortalized fibroblasts in a medium under conditions suitable for converting the fibroblast into an adipocyte and/or myocyte (See ¶0053-0055). The method can further comprise generating an edible meat product comprising adipocytes, myocytes, and endothelial cells (See ¶0056-0059). The culture medium can comprise M199, bFGF, IGF-1, Insulin, SCF, EGF, TGFß1, IL-11, PGE, BMP4, and any combination thereof (See ¶0190 and ¶0500, clause 6) The transferrin is present at a concentration of about 1-10 µg/ml (See ¶0369). Nahmias further discloses the system can be adapted to grow blood cells (See ¶0500, clauses 28 and 62).
Regarding claim 1: Nahmias discloses a method for culturing cells that form a cultured meat product (reads on cells requiring a supply of ferric iron) in a bioreactor. The method comprises culturing cells in a circulating perfusion bioreactor comprising dialysis system for filtering the perfusion solution that is recirculated which reads on culturing cells to be cultured in a perfusion bioreactor. The filter has a cut-off value of 30kDa which reads on less than 76 kDa. The cells are cultured in a medium comprising transferrin. In some embodiments the culture medium is M199 which comprises ferric nitrate (reads on a source of ferric iron) (See Millipore Sigma M199 Formulation).
Regarding claim 2: Following the discussion of claim 1 above, Nahmias discloses producing myocytes which reads on cultured cells requiring a ferric iron supply that contain myoglobin.
Regarding claim 3: Following the discussion of claim 1 above, Nahmias discloses culturing cells that form a cultured meat product which reads on the cultured cells requiring ferric iron supply are cultured meat cells.
Regarding claim 5: Following the discussion of claim 1 above, Nahmias discloses the culture medium further comprises bFGF, IGF-1, Insulin, SCF, EGF, TGFß1, IL-11, PGE, and BMP4 which reads on growth factors, cytokines, and/or hormones.
Regarding claim 6: Following the discussion of claim 1 above, Nahmias discloses a filter comprising a cut-off value of 30 kDa which reads on less than 50 kDa.
Regarding claim 7: Following the discussion of claim 1 above, Nahmias discloses embodiments using M199 medium which comprises Ferric nitrate which reads on a ferric iron salt.
Regarding claim 11: Following the discussion of claim 1 above, Nahmias discloses embodiments using a hollow-fiber dialyzer which reads on the bioreactor filter consists of hollow fibers.
Regarding claim 13: Following the discussion of claim 1 above, Nahmias discloses the transferrin is present at a concentration of about 1 to 10 µg/ml which reads on 10 to 3000 µg/ml.
Regarding claim 14: Following the discussion of claim 1 above, Nahmias discloses in some embodiments the filter has a cut-off value of 10 to 60 kDa which reads on less than 15 kDa.
Claim Rejections - 35 USC § 103
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.
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 1-3, 5-9, 11, and 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over Nahmias (US20200080050A1) as evidenced by Millipore Sigma (M199 Formulation) and in view of Chen (US20120264208A1).
The teachings of Nahmias and Millipore Sigma are set for above.
Nahmias anticipates claims 1-3, 5-7, 11, and 13-14.
Regarding claims 8 and 9: Following the discussion of claim 1 above, Nahmias discloses a method of culturing myocytes (reads on cells requiring a supply of ferric iron) in bioreactor in a medium comprising iron and transferrin.
Nahmias does not disclose the source of ferric iron is a complex of ferric iron and a chelating agent or a complex of ferric iron and citrate.
Chen discloses a culture medium for enhanced iron uptake in mammalian cell culture (See ¶0036). The culture media allows for the reduction of the amount of transferrin used in the medium compared to conventional media which is associated with advantages, including lower cost and reduced contamination (See ¶0036). The medium comprises an activator of non-transferrin bound iron (NTBI) and an iron chelate compound such as ferric ammonium citrate (See ¶0040 and claims 14-15). The culture medium can be used to culture myocytes (See claim 19 and ¶0010).
Given that Nahmias discloses a method of culturing myocytes which require ferric iron and Chen discloses a culture medium for culturing myocytes, comprising ferric ammonium citrate, an NTBI activator, and a reduced amount of transferrin, it would have been prima facie obvious to modify the culture method of Nahmias by using the culture medium of Chen. One would have been motivated to modify the culture method of Nahmias by using the culture medium of Chen because Chen discloses a medium that enhances iron uptake by cells, reduces cost, and reduces contamination. There is a reasonable expectation of success because Chen discloses the culture medium can be used to culture myocytes.
Claims 1-7, 10, 13, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Lipsitz (US20200370016A1 ) in view of Shwartz (PALL Life Sciences, Scientific & Technical Report, 2003).
Lipsitz discloses a method of generating a population of enucleated erythroid cells comprising culturing erythroid progenitor cells in a perfusion bioreactor (See claim 1). The culture method of Lipsitz comprises culturing cells in a first culture medium comprising about 50 µg/mL to 400 µg/mL transferrin and a second medium comprising IL-3, SCF, erythropoietin, transferrin, and insulin (See claims 44 and 64). The transferrin in the second medium can comprise about 1 µg/mL to 500 µg/mL holo-transferrin (See ¶0244). The first and second mediums further comprise L-glutamine, L-alanyl-L-glutamine, L-glycyl-L-glutamine, and N-acetyl-L-glutamine (See claims 37 and 83).Removal of the perfusion culture medium is performed mechanically using tangential flow filtration including one or more filters that have an average pore size of about 10 nm to about 6.0 µm (See ¶0263).
Regarding claims 1, 6, and 14: Lipsitz discloses a method of generating enucleated erythroid cells which reads on producing cultured cells requiring a supply of ferric iron. The method of Lipsitz comprise culturing erythroid progenitor cells in a perfusion bioreactor which reads on a step of culturing cells to be cultured in a perfusion bioreactor. The cells are cultured in a first and second medium comprising transferrin, which can be holo-transferrin (reads on a source of ferric iron). The culture system comprises a tangential flow filter for removal of the perfusion culture medium which reads on the culture medium is filtered at the bioreactor outlet by a filter.
Lipsitz does not disclose the filter has a cut-off value of less than 76 kDa.
Shwartz teaches the molecular weight cutoff (MWCO) of a membrane in a tangential flow filtration system should be determined based on the molecular weight (MW) of the target protein/molecule to be retained (See pg. 6, Step 2). Specifically, the MWCO should be 3 to 6 times lower than the MW of the target protein to be retained but higher than the MW of any molecule you are trying to pass.
Given that Lipsitz discloses a culture method comprising filtration through a tangential flow filter and Shwartz teaches the MWCO of the filter should be determined based on the MW of the proteins that are to be retained vs. molecules that should pass through the system, it would have been prima facie obvious to optimize the MWCO of the tangential flow filter in the method of Lipsitz based on which proteins should be filtered out, and arrive at the claimed sizes of less than 67 kDa, 50 kDa, or 15 kDa through routine experimentation. Where the general conditions of a claim are disclosed in the prior art it is not inventive to discover the optimum or workable ranges by routine experimentation. See MPEP2144.05(II)
Regarding claims 2 and 3: Following the discussion of claim 1 above, Lipsitz discloses culturing enucleated erythroid cells which reads on cells comprising hemoglobin.
Regarding claim 4: Following the discussion of claim 1 above, Lipsitz discloses culturing erythroid progenitor cells to produce a population of enucleated erythroid cells which reads on the cells to be cultured are erythroid progenitor cells and the cells requiring a ferric iron supply are cultured red blood cells.
Regarding claim 5: Following the discussion of claim 1 above, Lipsitz discloses culturing cells in a medium comprising L-glutamine, L-alanyl-L-glutamine, L-glycyl-L-glutamine, N-acetyl-L-glutamine , IL-3, SCF, erythropoietin, transferrin, and insulin which reads on the culture medium comprises nutrients as well as growth factors, cytokines, and/or hormones.
Regarding claim 7: Following the discussion of claim 1 above, Lipsitz discloses the transferrin in the medium can be holo-transferrin which reads on a complex of ferric iron and transferrin.
Regarding claim 10: Following the discussion of claim 1 above, the culture method of Lipsitz has a tangential flow filtration system to filter culture medium.
Regarding claim 13: Following the discussion of claim 1 above, the first culture medium comprising about 50 µg/mL to 400 µg/mL transferrin which reads on 10 to 3000 µg/mL.
Claims 1-7, 10, and 12-15 are rejected under 35 U.S.C. 103 as being unpatentable over Lipsitz (US20200370016A1), cited in IDS) in view of Shwartz (PALL Life Sciences, Scientific & Technical Report, 2003) and Pourcelot et al (BBA-Molecular Cell Research, 2015).
The teachings of Lipsitz and Shwartz are set forth above.
Lipsitz and Shwartz render claims 1-7, 10, 13, and 14 obvious.
Regarding claims 12 and 15: Following the discussion of claim 1 above, Lipsitz discloses a method of culturing erythroid progenitor cells and erythroid cells in a culture medium comprising transferrin.
Lipsitz does not disclose the saturation coefficient of the transferrin is maintained at a value greater than 10% or 50%.
Pourcelot discloses culturing CD34+ progenitor cells in medium depleted of iron which results in growth arrest (See Sec. 3.1). Supplementing the iron depleted medium with iron loaded transferrin rescues cell growth (See Sec. 3.2). Pourcelot further discloses it remains unclear how much transferrin delivered iron is needed to support proliferation of cells that must divide to maintain hematopoiesis or to fulfill specific functions (See. Sec: 1. Introduction).
Given that Pourcelot discloses loss of iron results in growth arrest of CD34+ progenitors which is rescued by iron loaded transferrin but it is unknown how much transferrin delivered iron is needed to support proliferation of cells, and Lipsitz discloses culturing cells with transferrin, it would have been prima facie obvious to optimize the saturation coefficient of the transferrin, in the method of Lipsitz, and arrive at the claimed values of greater than 10% or 50% through routine experimentation to maintain proliferation of the cultured cells. Where the general conditions of a claim are disclosed in the prior art it is not inventive to discover the optimum or workable ranges by routine experimentation. See MPEP2144.05(II)
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARISOL A O'NEILL whose telephone number is (571)272-2490. The examiner can normally be reached Monday - Friday 7:30 - 5:00 EST.
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/MARISOL ANN O'NEILL/Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633