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 .
The response filed 05/20/2026 has been received and entered. Claims 1, 5-6, and 10-15 remain pending, all of which have been examined on the merits.
Status of Prior Rejections/Response to Amendments
RE: Rejection of claims 1-3, 5-7, 11, and 13-14 under 35 U.S.C. 102 over Nahmias (US20200080050A1) as evidenced by Millipore Sigma (M199 Formulation).
Applicants amended claim 1 to require a step of culturing erythroid stem or progenitor cells or cells of an immortalized cell line of the erythroid lineage. Nahmias does not disclose culturing erythroid stem or progenitor cells or cells of an immortalized cell line of erythroid lineage.
The rejection over claims 1, 5-6, 11, and 13-14 is therefore withdrawn.
Claims 2, 3, and 7 have been cancelled, rendering their rejection moot.
RE: Rejection of claims 1-3, 5-9, 11, and 13-14 under 35 U.S.C. 103 over Nahmias (US20200080050A1) as evidenced by Millipore Sigma (M199 Formulation) and in view of Chen (US20120264208A1).
Applicants amended claim 1 to require a step of culturing erythroid stem or progenitor cells or cells of an immortalized cell line of the erythroid lineage. Nahmias and Chen do not disclose or suggest culturing erythroid stem or progenitor cells or cells of an immortalized cell line of erythroid lineage.
The rejection over claims 1, 5-6, 11, and 13-14 is therefore withdrawn.
Claims 2, 3, and 7-9 have been cancelled, rendering their rejection moot.
RE: Rejection of claims 1-7, 10, 13, and 14 under 35 U.S.C. 103 over Lipsitz (US20200370016A1 ) in view of Shwartz (PALL Life Sciences, Scientific & Technical Report, 2003).
Applicants amended claim 1 to require the limitation “wherein the source of ferric iron is a ferric iron salt, a complex of ferric iron and a chelating agent, or a complex of ferric iron and citrate”. Lipsitz and Shwartz do not disclose or suggest using an iron salt, a complex of ferric iron and a chelating agent, or a complex of ferric iron and citrate as a source of iron.
The rejection over claims 1, 5-6, 10, and 13-14 is withdrawn.
Claims 2-4 and 7 have been cancelled, rendering their rejection moot.
RE: Rejection of claims 1-7, 10, and 12-15 are under 35 U.S.C. 103 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).
Applicants amended claim 1 to require the limitation “wherein the source of ferric iron is a ferric iron salt, a complex of ferric iron and a chelating agent, or a complex of ferric iron and citrate”. Lipsitz, Shwartz, and Pourcelot et al do not disclose or suggest using an iron salt, a complex of ferric iron and a chelating agent, or a complex of ferric iron and citrate as a source of iron.
The rejection over claims 1, 5-6, 10, and 13-14 is withdrawn.
Claims 2-4 and 7 have been cancelled, rendering their rejection moot.
New Rejections
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.
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, 5, 6, 10, 11, 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) and Ponka et al (Blood, 1985).
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 culturing erythroid progenitor cells to produce a population of enucleated erythroid cells which reads on producing erythroid cells comprising a step of culturing erythroid progenitor cells. 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).
Additionally, Lipsitz does not disclose using a source of ferric iron that is a ferric iron salt, a complex of ferric iron and a chelating agent, or a complex of ferric iron and citrate.
Ponka et al teaches Fe-transferrin (i.e. iron loaded transferrin) is prepared by mixing ferric citrate with transferrin (See pg. 851, Sec. Studies with 59Fe).
Given that Lipsitz discloses a method culturing cells comprising holo-transferrin (i.e. iron loaded transferrin) and Ponka et al teaches iron loaded transferrin is prepared by combining ferric citrate and transferrin, it would have been prima facie obvious to substitute the holo-transferrin of Lipsitz with ferric citrate and transferrin in the method of Lipsitz. One would have expected ferric citrate and transferrin to work equivocally with transferrin in the method of Lipsitz because Ponka et al teaches ferric citrate and transferrin product iron loaded transferrin when combined. Substitution of one element for another known in the field, wherein the result of the substitution would have been predictable is considered to be obvious. See KSR International Co. V Teleflex Inc 82 USPQ2d 1385 (US2007) at page 1395.
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 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 11: Following the discussion of claim 1 above, Lipsitz discloses a method of culturing erythroid cells in a bioreactor culture system. The culture system comprises a tangential flow filter for removal of the perfusion culture medium.
Lipsitz does not disclose the type of filter used for tangential flow filtration.
Schwartz teaches TFF systems require a TFF device such as a capsule, cassette and holder, or hollow fiber module (See pg. 5 Sec. Tangential Flow Device Assembly). Schwartz thus teaches there is a finite number of filter types which can be used for TFF. Therefore, it would have been prima facie obvious to a person of ordinary skill in the art to select a hollow fiber module (i.e. a hollow fiber filter) as the TFF device for TFF in the method of Lipsitz. It has been held that "a person with ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense." See KSR International Co. v Teleflex, Inc. 82 USPQ2d 1385 at 1390.
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, 5, 6, 10-15 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), Ponka et al (Blood, 1985), and Pourcelot et al.
The teachings of Lipsitz, Shwartz, and Ponka et al are set forth above.
Lipsitz, Shwartz, and Ponka et al render claims 1, 5, 6, 10, 11, 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
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.
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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached at (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARISOL ANN O'NEILL/Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633
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