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 .
Applicant’s response on 12/15/2025 has been received and entered.
Claims 1-4, 6, 11-12, 20, 24, 29, 31-32 and 94-99 are pending, all of which have been considered on the merits.
Claim Objections
Claim 1 is objected to because of the following informalities: Claim 1(c) does not include a conjunction. The claim is therefore being interpreted as requiring limitations (i), (ii), and (iii) in the second culture medium. Appropriate correction is required.
Status of Prior Rejections/Response to Arguments
RE: Rejection of claims 2, 6, and 20 under 35 USC 112(b)
Applicants have amended claims 2, 6, and 20 to replace the terms Matrigel, Geltrex, E8 (shorthand for Essential 8), StemFlex, mTeSR, StemFit, E6 (shorthand for Essential 6), and Neurobasal medium with generic terminology. Amendments to the claims overcome the rejection. The rejection is withdrawn.
RE: Rejection of claims 1-4, 11, 12, 20, 22, 24, 27, 29, 31, and 32 under 35 USC 102 over Meyer, et al. (WO2012135621A2) as evidenced by Corning cell culture vessel guide.
Applicants traversed the rejection of record on the grounds that the instant claims, as amended, are anticipated by Meyer. Independent claim 1 has been amended to require a second culture medium with specific inhibitors of the BMP pathway and specific activators of the Notch pathway. Meyer does not disclose a second Medium comprising one or more activators of the Notch pathway listed in claim 1(c)(ii).
The rejection over claims 1-4, 11-12, 20, 24, 29, and 31-32 is therefore withdrawn.
Claims 22 and 27 have been cancelled, rendering their rejection moot.
RE: Rejection of claims 1-4, 6, 11, 12, 20, 22, 24, 27, 29, 31, and 32 under 35 USC 103 over Meyer et al. (WO2012135621A2) as evidenced by Corning cell culture vessel guide in view of Chen, (bioRxiv preprint, posted Oct 2019).
Applicants traversed the rejection of record on the following grounds.
I. The cited references, alone or in combination, fail to disclose or suggest methods of producing, in culture, radial glia-like cells recited in the instant claims, as amended. Specifically, Applicants assert that Meyer et al teaches a method comprising three different culture mediums and that there is no indication of the “Neural Transition Media” and “Neural Induction Media” containing a BMP inhibitor, Notch activator, and IL-6.
In response, the argument has been fully considered. Example 3 teaches “Neural transition media” and “Neural induction media” are used during the priming step. Meyer teaches priming, aggregate formation and/or further differentiation medium can comprise IL-6 and the cell priming or differentiation environment can also contain, BMP inhibitors such noggin, follistatin, chordin, and gremlin, and molecules that activate signaling through Notch receptor family including proteins of the delta like and Jagged families (See ¶0083-¶0085). Therefore, “neural transition media” and “neural induction media” can comprise a BMP inhibitor, Notch activator, and IL-6.
However, the amendments to the claims require the Notch activator to be Jag1, Jag2, DLL1, DLL2, or DLL3. Meyer does not specify the Delta or Jagged family member used in the medium. Therefore, amendments to the claim overcome the rejection of record.
II. The various teachings in Meyer et al disclose many potential options for any of the recited medias and therefore would not lead a person of ordinary skill in the art to the claimed methods.
In response, the argument has been fully considered but is not found persuasive. While Meyer et al discloses various embodiments of culture medias, the medias disclosed by Meyer et al render the claimed method obvious.
III. There are fundamental differences between the methods of Meyer et al and the methods of the instant application.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., the differences between methods for producing neural progenitors and radial glia-like cells) are not recited in the rejected claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Furthermore, the specification of the instant application teaches radial glia-like cells are “cells exhibiting at least some properties of radial glia cells occurring during vertebrate embryonic development” (See ¶0028). The neural progenitor cells of Meyer et al express Pax6 and CD133 which are markers of radial glia cells. The neural progenitor cells of Meyer et al are also capable of differentiating to astrocyte-like cells. Expressing markers of radial glia cells and differentiating into astrocyte-like cells read on at least some properties of radial glia cells occurring during vertebrate embryonic development. Therefore, the neural progenitor cells of Meyer et al. read on radial glia-like cells. Additionally, Meyer et al discloses methods which render the methods, as claimed, obvious (See rejection below).
The rejection over claims 1-4, 6, 11-12, 20, 24, 29, and 31-32 is withdrawn.
Claims 22 and 27 have been cancelled, rendering their rejection moot.
New / Maintained Rejections
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.
Claim 95 is 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.
Claim 95 recites the limitation "the one or more Platelet-Derived Growth Factor protein"" in lines 1-2. There is insufficient antecedent basis for this limitation in the claim. For the purpose of compact prosecution, claim 95 will be interpreted as depending from claim 24.
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 1-4, 6, 11 12, 20, 24, 29, 31, 32, 98, and 99 stand rejected under 35 U.S.C. 103 as being unpatentable over Meyer et al. (WO2012135621A2) as evidenced by Corning cell culture vessel guide, and Stupnikov et al (elife, 2019).
Meyer et al. discloses a method for differentiating pluripotent stem cells of human, mouse or other mammalian origin (See ¶0016) into progenitors of neural lineage cell (See ¶00151). The progenitors express one or more detectable markers including Pax6 and CD133 (read on markers of radial glia) and can be further differentiated into astrocytes (See ¶00151 and claim 22). The progenitor cells which express radial glia markers Pax6 and CD133 and are capable of differentiating into astrocytes. The method comprises seeding the pluripotent cells at 104 – 1010 cells/mL in a T150 flask, on Matrigel, in TeSR media supplemented with blebbistatin (reads on ROCK inhibitor) for days -4 and -5 (reads on 2 days) (¶00127 and ¶00172). Other pluripotent cell culture media such as E8 or mTeSR can be used (See ¶00171-00172). On day -3, the cells are transitioned to DMEM-F12 neural induction media and the media is replaced with full DMEM-F12 media on day -2 (See ¶00172). On days 1-6 the spent media is aspirated and replaced with fresh DMEM-F12 (See ¶00172). The cells are maintained in the DMEM-F12 neuronal induction media for 14 days (See ¶00174). Additional factors may be added in priming, aggregate formation and/or further differentiation medium to promote neural stem/ progenitor proliferation and survival. These neurotrophic factors include interleukin-6, CNTF, and LIF (See ¶0085). Additionally the cell priming or differentiation environment can also contain PDGFs, BMP inhibitors such noggin, follistatin, chordin, and gremlin, and molecules that activate signaling through Notch receptor family including proteins of the delta like and Jagged families (See ¶0083). Meyer et al. also discloses cells are typically passaged when 70-100% confluent in order to enable cells to survive and grow under cultured conditions for extended periods of time (See ¶00117). Additionally, Meyer teaches passage intervals can be optimized by altering the split ratio and a passage ratio of 1:3 can be used to split the cells every 4-7 days (See ¶00118).
Regarding claims 1-4, 12, 24, 29, and 99: The specification of the instant application teaches radial glia-like cells are “cells exhibiting at least some properties of radial glia cells occurring during vertebrate embryonic development” (See ¶0028). Meyer et al. discloses a method for differentiating mammalian (reads on vertebrate) stem cells into neural progenitors expressing Pax6 and CD133 and can further differentiate into astrocytes. Expressing markers of radial glia cells and differentiating into astrocyte-like cells read on at least some properties of radial glia cells occurring during vertebrate embryonic development. Therefore, the neural progenitor cells of Meyer et al. read on radial glia-like cells.
The method of Meyer et al. requires seeding pluripotent stem cells on Matrigel (reads on substrate-coated surface) at a cell density 104 – 1010 cells/mL of TeSR, mTeSR, or E8 media + blebbistatin (reads on Rock inhibitor) in a T150 flask. A T150 flask has a surface area of 150cm2 and holds 30-45 mL of culture media. Therefore, the pluripotent cells of Meyer et al. can be seeded at a density of 2000 cells/cm2 ((104 cells/mL x 30 mL)/150cm2 = 2000cells/cm2) which reads on 1000-100,000 cells/cm2. The pluripotent stem cells are cultured in the TeSR media (reads on first culture medium) for 2 days (reads on incubating in the first culture medium for 12-48 hours). The cells are then transitioned to a neural induction media comprising DMEM-F12 where they are maintained for 14 days which reads on the second culture medium comprises culturing for at least 5-20 days. The second culture media can further comprise neurotrophic factors such as interleukin-6, CNTF, and LIF, BMP inhibitors such as Noggin, Follistatin, Chordin, or Gremlin (reads on claim 99), Notch activators such as proteins of the Delta like and Jagged families, and PDGF.
While Meyer et al teaches the neural induction media (second media) contains a Jagged protein, Meyer et al does not explicitly disclose the use of Jag1or Jag2. However, the Jagged family of proteins consists of Jag1 and Jag2 (See Stupnikov et al, Introduction). Therefore, it would be obvious to use Jag1 or Jag2 as the Jagged family in the method of Meyer et al because the Jagged family only consists of Jag1 and Jag2. 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 11: Meyer et al. teaches a method for producing neural progenitor cells by culturing pluripotent stem cells in a first media of TeSR, mTeSR, or E8 with a ROCK inhibitor for two days. Then culturing in a second media, comprising DMEM-F12, PDGF, BMP inhibitors, Notch activators, and interleukin-6 cytokines for 14 days. Given that Meyer et al teaches producing neural progenitor cells which express Pax 6 and CD133, which read on radial glia-like cells by day 14 after start of 2nd culture medium, there is reasonable basis to conclude that there are at least some radial glia (CD133 or Pax6) or neural stem cell (Pax6) in the culture by day 10 as the cells are gradually differentiating.
Regarding claims 31-32: Meyer et al. discloses while culturing in the neural induction medium (second medium) the spent media is aspirated and replaced with fresh media daily on days 1-6 (reads on changing the second culture medium approximately every 20-28 hours) and the cells are passaged when they become 70-100% confluent.
Regarding claim 98: Following the discussion of claims 1 and 32 above, Meyer et al teaches a method producing radial glia cells comprising a passaging step every 1-6 days once cells become 70-100% confluent. Meyer et al further teaches the ratio at which cells are passaged can be altered in order to optimize the interval at which the cells are passaged and cells passaged at a ratio of 1:3 can be passaged every 4-7 days. Furthermore Meyer et al teaches passaging cells enables cells to survive and grow for extended periods of time.
Meyer et al does not teach the cells are passaged at a 1:3 to 1:5 ratio of confluent cells or that culturing in the second medium comprises 3-7 passaging steps.
Although Meyer et al does not teach passaging cells in the second medium at a ratio of 1:3 of confluent cells, Meyer teaches the ratio at which cells are split affects how often the cells need to be passaged. Therefore, it would have been prima facie obvious to optimize, to a person of ordinary skill in the art to optimize the ratio at which the cells are split and arrive at the claimed ratio of 1:3 in order to passage the cells every 4-7 days. Additionally, it would have been prima facie obvious to optimize the number of times passaging occurs, and arrive at the claimed 3-7 passages, in order to maintain the survival of the cells for an extended period of time. 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)
Claims 1-4, 6, 11 12, 20, 24, 29, 31, 32, 98, and 99 stand rejected under 35 U.S.C. 103 as being unpatentable over Meyer et al. (WO2012135621A2) as evidenced by Corning cell culture vessel guide, in view of Chen, (bioRxiv preprint, posted Oct 2019).
The teachings of Meyer et al. are set forth above.
Meyer et al renders claims 1-4, 11, 12, 20, 24, 29, 31, 32, 98, and 99 obvious.
Regarding claim 6: Meyer teaches a method for differentiating pluripotent stem cells into neural lineage progenitors. The method comprises culturing the pluripotent cells in a first and second media. Meyer et al further teaches pluripotent stem cells, especially human ES cells and iPS cells are vulnerable to apoptosis upon cellular detachment and dissociation and ROCK inhibitors have been found to increase survival of dissociated pluripotent stem cells (See ¶00102-00103). Additionally, Meyer et al. teaches additional factors may be added to promote neural stem/progenitor proliferation and survival (See ¶0085).
Meyer et al. does not teach the use of Chroman 1, Emricasan, trans-ISRIB, putrescine, spermine, and spermidine in the first Media.
Chen teaches the combination of 50nM (reads on 4 nM – 80µM) Chroman 1, 5µM (reads on 100nM to 80µM) Emricasan, Polyamines, and 0.7µM (reads on 50nM to 80µM) Trans-ISRIB (CEPT) enhance cell survival of genetically stable hPSCs by blocking several stress mechanisms (See pg. 34 section: Small molecule chemical compounds and abstract). The polyamines are a mixture of 40ng/mL (reads on 453.77 nM which is in the range of about 0.5nM to 1mM) putrescine, 4.5 ng/mL (reads on 30.98 nM which is in the range of about 0.5nM to 1mM) spermidine, and 8ng/mL (reads on 39.54 nM which is in the range of about 0.5nM to 1mM) spermine (See pg. 5 first paragraph).
Given that Chen teaches adding 50nM Chroman 1, 5 µM Emricasan, 0.7µM Trans-ISRIB, 0.5nM putrescine, 30.98mM spermidine, and 39.54nM spermine enhances survival of pluripotent stem cells and Meyer et al. teaches additional factors may be added to the media to promote survival, it would have been prima facie obvious to add the composition of Chen to the first media of Meyer et al. in order to enhance survival of the pluripotent stem cells.
Claims 1-4, 6, 11 12, 20, 24, 29, 31, 32, 94, 98, and 99 stand rejected under 35 U.S.C. 103 as being unpatentable over Meyer et al. (WO2012135621A2) as evidenced by Corning cell culture vessel guide, in view of Kuwahara et al (Scientific Reports, 2019)
The teachings of Meyer et al. are set forth above.
Meyer et al renders claims 1-4, 11, 12, 20, 24, 29, 31, 32, 98, and 99 obvious.
Regarding claim 94: Following the discussion of claim 1 above, Meyer et al discloses the method of producing radial glia-like cells comprising a first medium which can include BMP inhibitors.
Meyer et al does not teach the BMP inhibitor comprises 2 nM to 40 µM LDN-193189.
Kuwahara et al teaches a method of differentiating pluripotent stem cells to neural retina progenitors with radial glia-like morphology (reads on radial glia-like cells) (See Sec. Introduction). The method comprises a step of culturing hPSCs in a medium with 100 nM LDN193189 for 18-30 hours prior to differentiation (See Sec. Retinal differentiation from Ff-hPSCs by the preconditioning, d0-SAG and BMP methods).
Given that Meyer et al and Kuwahara et al both teach methods of differentiating pluripotent stem cells into radial glia-like cells comprising steps of culturing in a medium comprising a BMP inhibitor prior to differentiation, it would have been prima facie obvious to substitute the BMP inhibitor of Meyer et al with 100 nM of LDN193189 (reads on 2 nM to 40 µM) , as disclosed by Kuwahara et al, in the method of Meyer et al. One would have expected the LDN193189 of Kuwahara et al to work equivocally with the BMP inhibitor of Meyer et al, in the method of Meyer et al because LDN193189 is a BMP inhibitor. 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.
Claims 1-4, 6, 11 12, 20, 24, 29, 31, 32, 94, 98, and 99 stand rejected under 35 U.S.C. 103 as being unpatentable over Meyer et al. (WO2012135621A2) as evidenced by Corning cell culture vessel guide in view of Walsh et al (Cell Transplant, 2017).
The teachings of Meyer et al. are set forth above.
Meyer et al renders claims 1-4, 11, 12, 20, 24, 29, 31, 32, 98, and 99 obvious.
Regarding claim 94: Following the discussion of claim 1 above, Meyer et al discloses the method of producing radial glia-like cells comprising a first medium which can include BMP inhibitors.
Meyer et al does not teach the BMP inhibitor comprises 2 nM to 40 µM LDN-193189.
Walsh et al teaches a method of differentiating hiPSCs to neural progenitors (See Sec. Differentiation of HiPSCs into human VSNPs (hVSNPs)). The method of Walsh et al comprises culturing hiPSCs in Essential 6 medium supplemented with 250 nM of LDN-193189. Walsh further teaches LDN-193189 is sufficient for neural induction in hiPSCs (See abstract).
Given that Meyer et al teaches a method of differentiating pluripotent stem cells to radial glia-like neural progenitors and Walsh et al teaches 250 nM of LDN-193189 is sufficient for neural induction in hiPSCs, it would have been prima facie obvious to include 250 nM (reads on 2 nM – 40 µM) of LDN-193189 in the priming medium of Meyer et al. One would have been motivated to include 250 nM of LDN-193189 in the priming medium of Meyer et al in order to initiate neural induction in pluripotent stem cells. There is a reasonable expectation of success because Walsh teaches 250 nM of LDN-193189 is sufficient to induce neural induction in hiPSCs.
Claims 1-4, 6, 11 12, 20, 24, 29, 31, 32, 95, 98 and 99 stand rejected under 35 U.S.C. 103 as being unpatentable over Meyer et al. (WO2012135621A2) as evidenced by Corning cell culture vessel guide in view of Gorris (Glia, 2015)
The teachings of Meyer et al. are set forth above.
Meyer et al renders claims 1-4, 11, 12, 20, 24, 29, 31, 32, 98, and 99 obvious.
Regarding claim 95: Following the discussion of claims 1 and 24 above, Meyer et al discloses the method of producing radial glia-like cells comprising a second medium which can comprise PDGF.
Meyer et al does not teach the PDGF is PDGF-AA, PDGF-BB, or PDGF-AB or that the concentration of PDGF is 1ng/mL-800ng/mL.
Gorris teaches a method of differentiating pluripotent stem cells to Oligodendrocytes with an intermediate step of differentiating the cells to radial glia-like cells. Gorris further teaches culturing the radial glia like cells comprising 10ng/mL of PDGF-AA results in differentiation to oligodendrocytes (See Secs. RGL-NPCs can be Efficiently Differentiated into Oligodendroglia in vitro and Cell culture).
Given that Meyer et al teaches a method of producing radial glia-like cells and Gorris teaches radial glia like cells can be differentiated to oligodendrocytes using culture medium comprising 10 ng/mL of PDGF-AA, it would have been prima facie obvious to ad 10ng/mL of PDGF-AA to the culture medium of Meyer et al, in order to further differentiate the cells into oligodendrocytes. One would have been motivated to add 10 ng/mL of PDGF-AA to the culture medium of Meyer et al in order to differentiate the radial glia like cells to oligodendrocytes. There is a reasonable expectation of success because Gorris et al teaches radial glia-like cells can be differentiated to oligodendrocytes using a medium comprising PDGF-AA.
Claims 1-4, 6, 11, 12, 20, 24, 29, 31, 32, 96, 98 and 99 stand rejected under 35 U.S.C. 103 as being unpatentable over Meyer et al. (WO2012135621A2) as evidenced by Corning cell culture vessel guide in view of Blackwood (Neuroscience, 2019).
The teachings of Meyer et al. are set forth above.
Meyer et al renders claims 1-4, 11, 12, 20, 24, 29, 31, 32, 98, and 99 obvious.
Regarding claim 96: Following the discussion of claim 1 above, Meyer et al discloses the method of producing radial glia-like cells comprising a second medium with Jagged family members.
Meyer et al does not disclose the Jagged family member is Jag1 and is present at a concentration of 1ng/mL – 800 ng/mL.
Blackwood teaches loss of Jag1 during neural development leads to reduced numbers of radial glia cells because Jag-1 promotes self-renewal of radial glia cells (See Sec. Discussion).
Given that Meyer et al teaches a method of producing radial glia-like cells in culture and Blackwood teaches Jag-1 promotes self-renewal of radial glia cells, it would have been prima facie obvious to include Jag1 in the second medium of Meyer et al in order to promote self-renewal of the radial glia like cells. One would have been motivated to use Jag1 in the culture medium of Meyer et al in order to maintain the population of radial glia-like cells through self-renewal. There is a reasonable expectation of Success because Blackwood teaches Jag1 promotes self-renewal of radial glia cells.
Additionally, Given that Blackwood teaches loss of Jag1 reduces the number of radial glia cells, it would have been prima facie obvious, to a person of ordinary skill in the art, to optimize the amount of Jag1 in the culture medium, and arrive at the claimed range of 1 ng/mL – 800 ng/mL, through routine experimentation in order to optimize the number of radial glia-like cells in the culture. 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).
Claims 1-4, 6, 11-12, 20, 24, 29, 31, 32, and 97-99 stand rejected under 35 U.S.C. 103 as being unpatentable over Meyer et al. (WO2012135621A2) as evidenced by Corning cell culture vessel guide in view of Bonaguldl et al (Development, 2005).
The teachings of Meyer et al. are set forth above.
Meyer et al renders claims 1-4, 11, 12, 20, 24, 29, 31, 32, 98 and 99 obvious.
Regarding claim 97: Following the discussion of claims 1 and 97 above, Meyer et al teaches a method of differentiating pluripotent stem cells to radial-glia like cells. The method of Meyer et al can comprise a second culture medium comprising IL-6, CNTF, and LIF.
Meyer et al does not teach one or more of the CNTF or LIF are present at a concentration of 1ng/mL-800ng/mL.
Bonaguldl et al teaches LIF and BMP signaling promote differentiation of neural stem/progenitor cells into GFAP+ progenitors (reads on radial glia-like cells) and regulate morphology, cell-cycle exit, maintenance of stem/progenitor traits vs differentiation into astrocytes (See Introduction and Table 1).
Given that Meyer et al teaches a method for producing radial glia-like cells which can be differentiated into astrocytes and Bonaguldl et al teaches LIF signaling can regulate whether neural progenitors are maintained in a progenitor state or differentiated into astrocytes, it would have been prima facie obvious to optimize the concentration of LIF in the culture medium of Meyer et al and arrive at the claimed concentration of 1ng/mL-800ng/mL in order to optimize the desired level of progenitor vs astrocyte cells in the culture. 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
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/MARISOL ANN O'NEILL/Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633