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 .
This action is in response to the papers filed 06/15/2026.
Claims 52-53, and 55-71 are pending in the application. Claims 52-53, 55-56, 59, 64, 66, and 68-69 are amended, claim 54 is canceled, and no new claims are added as set forth in the claim set filed 06/15/2026. Claims 52, 64, 65, 66, 68, 70 and 71 are independent.
Therefore, claims 52-53 and 55-71 are examined on the merits.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/CA2021/051239 filed September 08, 2021.
Applicant’s claim for the benefit of a prior-filed parent provisional applications 63/075,575 filed September 08, 2020, under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Thus, the earliest possible priority for the instant application is September 08, 2020.
Claim Interpretation
Claim 53 recites the term “[AC1.1]” which has not been recited previously in any claim set or in the specification. However, the brackets are interpreted as removing the term and therefore, the term will not be examined.
Response to arguments
Withdrawn objections/ Rejections in response to Applicants’ arguments or amendments
Claim Objections
The objection of Claim 52 is withdrawn due to the amendments made to spell out acronyms.
Claim Rejections - 35 USC § 112
The previously set forth rejection of claims 52-71 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn.
Applicant’s arguments and amendments filed 06/15/2026 have been considered and are persuasive. Applicants have amended claims 53, 59, and 66 to remove the phrase "such as." Claims 52, 53, 64, 66, and 68 have been amended to proper Markush form. Claim 66 has been amended to remove the term "essentially." Claim 69 has been amended to remove the incorporation by reference. Claim 53 has been amended to remove the term "primed."
Maintained objections/ Rejections in response to Applicants’ arguments or amendments
Claim Rejections - 35 USC § 102
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.
Claim 52, 58-59, and 62-65 remain rejected under 35 U.S.C. 102(a)(1) as being anticipated by Fehlings (WO2019/023793; published February 2019; Applicant’s own work).
Regarding claim 52, Fehlings teaches a method of making neural progenitor cells (spNPCs) having spinal identity comprising producing first caudalized NPCs which includes steps of passaging NPCs and incubating the NPCs in culture media supplemented with a RAR agonist such as Retinoic Acid (RA) to produce caudalized NPCs (Fig 1A and 10A, para. 0015, 0046).
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As seen in Figure 10D below, the caudalized cells express reduced levels of Otx2 levels compared to that of unpatterned NPCs, although the term“posteriorized” NPCs are not explicitly stated, these are viewed as an intermediary while the caudalized NPCs are produced from unpatterned NPCs exposed to retinoic acid to eventually produce caudalized NPCs in the same population (para. 0046).
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As retinoic acid is utilized in both the claimed invention and caudalization of Fehlings, the same method steps yield the same results. Therefore, the caudalized cells would express reduced levels of Otx2 levels compared to the posteriorized cells. Fehlings additionally teaches passaging the caudalized NPCs in suitable culture media supplemented with retinoic acid and an EGFR agonist (para. 0015, step g). Fehlings teaches ventralization after caudalization utilizing a suitable media and then culturing in the presence of a FGF agonist such as FGF2, EGFR, PDGFR agonist wherein the FGF2 is at an amount of 20ng/ml (para. 0015, steps h-I, para. 0064, 0079, 00160). Fehlings discloses “the term "PDGFR agonist" as used herein means any protein or small molecule that can activate the PDGF receptor A and/or PDGF receptor B (e.g. molecules that bind to PDFGR, induce the dimerization of the receptor and activate the signaling PI3K pathway and STAT1/3 pathways) including any members of the PDGF family such as PDGF- A, -B, -C and -D, and either homo- or heterodimers (e.g. PDGF-AA, -AB, -BB, -CC, -DD). In addition to PDGF, PDGF analogues are known and include for example 740 Y-P (PDGFR 740Y-P)” (para. 0070).
While Fehlings does not teach explicitly that the method is for producing spinal identity neural progenitor cells (spNPCs), the progenitor cells are made through the same methods steps as the invention, therefore, having the same properties.
Regarding claim 58, Fehlings teaches a ROCK inhibitor added after each passage in the first 24 hours (para. 0033).
Regarding claim 59, Fehlings teaches that retinoic acid (RA) is used (para. 0015).
Regarding claim 62 and 63, Fehlings teaches the FGF2 agonist is FGF2 and EGF receptor agonist is EGF (para. 0015, 0065).
Regarding claim 64, the isolated cell population is made by the method of claim 52 which is anticipated by Fehlings, therefore, the isolated cell population claimed is also anticipated by Fehlings. Moreover, Fehlings teaches that the population of cells made can be isolated, purified or diluted (para. 00143).
Regarding claim 65, Fehlings teaches the isolated cell population of claim 64 as discussed above. Morever, Fehlings teaches spinal cord injury treatment or demyelination disease (i.e. neurodegenerative) as uses for the isolated cells which would be administered to a subject (para. 0027, 00150-151).
Therefore, by teaching all of the above claimed limitations, the invention is anticipated by Fehlings.
In response to Applicant’s arguments and amendments filed 06/15/2026,
Applicants’ arguments and amendments filed 06/15/2026 have been considered, however they are not persuasive.
Applicant argues that Fehlings does not teach the full spinal spNPC protocol as claimed involving particular components such as EGFL7 priming and maintaining nor the patterning steps or the use of Wnt with RAR during the patterning, or the use of 750Y-P together with the FGF-EGF pathway to stablilize or expand the final spNPC. Applicant further argues that “EGF-L7 is not a conventional neural patterning factor. Its incorporation in the posteriorization phase, alongside FGF2 and FGF8, to shift NPC identity by modulating Notch signaling is a novel application. None of the cited prior art references describes this specific use of EGF-L7 to induce posteriorization or caudal fate. The claimed method results in NPCs with elevated Hox gene expression and downregulated brain markers (Gbx2, Otx2, FoxG1)” (Remarks p. 8).
The examiner states that the arguments are directed towards elements not recited in the claims rejected under Fehlings as a 102 reference. Independent claim 52 does not recite the EGFL7 priming step or EGFL7 at all, which if critical to the making of the claimed cells, should be included in the independent claim for an artisan to make the invention. Moreover, claim 52 does not require “the use of Wnt activation together with RAR signaling during spinal patterning/caudalization” or use of unique combinations “ EGF-L 7 and 740Y-P” to stabilize spinal identity, as applicants argue. Hence the argument is not persuasive as they argue limitations that are not present in the claims. As Applicant argues that it is a crucial part to be utilized alongside other components, it is advised that EGFL7 be amended into the independent claim in order to overcome the 102 rejection. The 102 rejection reads on each and every limitation of claim 52 as previously and currently presented.
Claim Rejections - 35 USC § 103
Claims 53 and 55 remain rejected under 35 U.S.C. 103 as being unpatentable over Fehlings (WO2019/023793; published February 2019; Applicant’s own work) in view of Bicker (2017, Nat. Commun. 8, 15922).
This rejection has been modified as necessitated by Applicant’s arguments and amendments filed 06/15/2026.
As discussed above in the 102 rejection and incorporated herein in its entirety, Fehlings teaches a method of making spNPCs via making caudalized NPCs from iPSC derived unpatterned NPCs. Moreover, Fehlings teaches that unpatterned NPCs are subjected to culture with one or more of FGFR agonists such as FGF2 and FGF8 (para. 0064, 0078) and anticipates claims 52, 58-59, and 62-65.
However, regarding claim 53, Fehlings does not teach priming unpatterned NPCs through the method step of adding EGF-L7 agonist to culture media to achieve a primed unpatterned NPCs which stay in the ectodermal cell fate expressing markers such as Pax6 and Sox1 or supplementing the primed unpatterned NPCs in culture media with FGF2 and FGF8 as required in claim 53.
Bicker teaches that the addition of EGFL7 pushes activated NSCs (neural stem cells) towards quiescence and neuronal progeny such as NPCs and activated NSCs towards differentiation through promoting the Notch signaling system (Abstract, p. 7, 2nd column).
It would have been obvious to the ordinary artisan that the EGF-L7 of Bicker could have been applied to the method of Fehlings, to produce primed unpatterned NPCs from the unpatterned NPCs with a reasonable expectation of success. As Fehlings teaches a process of differentiation, an artisan would have been motivated to utilize a protein such as EGF-L7 known to induce differentiation and promote the Notch signaling system. As discussed above, as each and every method step is the same, the same results will occur such as posteriorized NPCs expressing higher levels of at least one Hox gene, expressing Sox1 and Pax6 and lower levels of at least one of the brain markers such as Gbx2, Otx2 and FoxG1 compared to unpatterned NPCs.
Regarding claim 55, as discussed above, Fehlings and Bicker make obvious claim 53. Moreover, Fehlings discloses culturing cells differentiating from hiPSCs in the presence of DLL4 (i.e. notch signaling activator) with EGF and FGF2 (para. 000167).
Therefore, the invention would have been obvious to one of ordinary skill in the art at the time of the effective filing date.
Claims 56 and 57 remain rejected under 35 U.S.C. 103 as being unpatentable over Fehlings (supra) in view of Bicker (supra) as applied to claim 53 above, and in further view of Plaistead (PLoS ONE 11(6): e0157620), Hung (“ Formation of Embryonic Bodies to Produce Neural Stem Cells from iPSCs Using the Corning® Spheroid Microplate” 2018) and Ding (J. Cell. Physiol. 225: 417–428, 2010)
This rejection has been modified as necessitated by Applicant’s arguments and amendments filed 06/15/2026.
As discussed above in the 103 rejection and incorporated here in its entirety, Fehlings and Bicker make obvious a method of making spNPCs via making caudalized NPCs from iPSC derived unpatterned NPCs which are primed via EGF7 and a notch signaling receptor.
Regarding claim 56, Fehlings teaches that the iPSCs are passaged and incubated in an iPSC media for at least about 2 days (para. 0015, step a). Regarding step b, BMP inhibitors and dual SMAD inhibitors are added on day 2 (Fig 3). Regarding step d, rosettes are produced through the method of Fehlings after culturing the cells in NIM with a FGF2 agonist wherein dual SMAD and BMP inhibitors are removed on day 9 (cultured for 7 days) (para. 00160, Step 9; Figure 3). Regarding the limitation wherein the BMP inhibitor or dual SMAD inhibitors are removed from the media on about day 2, to produce unpatterned NPCs, it is interpreted in light of the specification that because day 2 is when the BMP inhibitor is placed, the claim is referring to day 2 of the inhibitors presence not day 2 of the culture (see protocol on p. 37), day 4 overall.
However, Fehlings and Bicker do not teach steps b and c wherein the iPSC culture media lacks a FGF2 agonist and wherein the NIM lacks the FGF2 agonist. The references also do not teach the production of embryoid bodies which are cultured to produce neural rosettes in the presence of BMP inhibitors for 2 days.
Plaistead teaches a method wherein hiPSC form embryoid bodies (EBs) on the fifth day without FGF supplementation in the media which form rosette structures when supplemented with bmp inhibitors then cultured in the presence of FGF to obtain NPCs (p. 3, Derivation and maintenance).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date to modify the teachings of Fehlings and Bicker with the teachings of Plaistead to arrive at the claimed method involving steps lacking FGF to achieve embryoid bodies with a reasonable expectation of success (current claim 56, steps b. and c, in part.). An artisan would be utilizing a known technique to modify the method of producing NPCs from hiPSCs.
However, the above references do not teach EB formation in 2 days.
Hung teaches EB formation in 2 days from iPS utilizing an essential 8 medium that does not contain FGF (Protocol 1).
Therefore, it would have been obvious to one of ordinary skill in the art at the time of the effective filing date to modify the teachings of Fehlings, Bicker, Plaistead with the teachings of Hung to arrive at the claimed method involving steps able to achieve embryoid bodies in 2 days of culture with a reasonable expectation of success. An artisan would be utilizing a known technique to modify the method of producing NPCs from hiPSCs. As the EB formation is a smaller 2 day time period, it would be obvious to one of ordinary skill in the art to remove bmp inhibitors at a shorter time period such as 2 days instead of the 7 days of Fehlings.
Regarding claim 57, Fehlings, Bicker, Plaistead and Hung make obvious the method of claim 56 as discussed above. Moreover, Fehlings show a BMP inhibitor, TGFbeta inhibitor, FGF2 agonist combined in their induction media.
However, these inhibitors are not present in the iPSC media, nor is a Wnt inhibitor utilized.
Ding teaches FGF-2 directly regulates activity to maintain ESC and iPS cells in an undifferentiated state (p. 422, 1st paragraph). Both Wnt inhibitor (DKK-1) and FGF-2 were cultured together and no significant change was found from regulating activity of TCF/LEF (p. 427, 1st paragraph).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date to put a BMP inhibitor, TGFP inhibitor, FGF2 agonist, and Wnt inhibitor in the media of step a) as some are known to be part of neural differentiation in figure 3 of Fehlings (See FGF, TGFbi, BMPi, Noggin) in addition to a Wnt inhibitor as taught by Ding with a reasonable expectation of success. An artisan would be motivated to do so as all of Fehlings inhibitors and FGF are applied to the media after the iPSC media in the method, therefore it would be obvious to one of ordinary skill in the art to apply the same inhibitors to the step previous in culturing iPSCs to the same end result of NPCs. Additionally, Ding teaches both Wnt inhibitor (DKK-1) and FGF-2 were cultured together regulating activity of TCF/LEF. Therefore, Wnt inhibitors and FGF-2 are known to work together to maintain iPSCs.
Therefore, the invention would have been obvious to one of ordinary skill in the art.
Claims 60 and 61 are rejected under 35 U.S.C. 103 as being unpatentable over Fehlings (supra) in view of Bicker (supra) as applied to claim 52 above, and in further view of Bejoy (Organogenesis, 12:1–15, 2016)
This rejection has been modified as necessitated by Applicant’s arguments and amendments filed 06/15/2026.
As discussed above in the 103 rejection and incorporated here in its entirety, Fehlings and Bicker make obvious a method of making spNPCs via making caudalized NPCs from iPSC derived unpatterned NPCs which are primed via EGF7 and a notch signaling receptor.
However, regarding 60 and 61, these references do not teach wherein the posteriorized NPCs are incubated in culture media supplemented with a Wnt signaling activator in addition to the RAR agonist, wherein the Wnt signaling activator is Wnt3a, AZD2858, Wnt agonist 1, CP21R7 (CP21), Wnt or BML-284 hydrochloride.
Bejoy teaches due to the neural patterning effect, Wnt signaling can efficiently promote motor neuron differentiation from hPSCs, in combination with caudalization factor retinoic acid (RA) and ventralization factor SHH. Wnt signaling may elevate the threshold level of SHH signaling to enrich motor neural progenitors. (p. 4, 1st column). Wnt activation induces a caudal fate of neural progenitors that more easily differentiate into motor neurons (p. 4, 1st column). Known wnt activators/agonists are wnt3a (Table 2).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date to add wnt3a as taught by Bejoy at the time of introducing RA in Fehlings and Bicker with a reasonable expectation of success. An artisan would have been motivated to do so as the RA is being utilized to caudalize the NPCs in Fehlings and Bejoy teaches wnt activation induces caudal fate.
Therefore, the invention would have been obvious to one of ordinary skill in the art.
Claims 66-71 are rejected under 35 U.S.C. 103 as being unpatentable over Fehlings (WO2019/023793; published February 2019; Applicant’s own work) in view of Bicker (2017, Nat. Commun. 8, 15922), Plaistead (PLoS ONE 11(6): e0157620), Ding (J. Cell. Physiol. 225: 417–428, 2010) and Bejoy (Organogenesis, 12:1–15, 2016)
This rejection has been modified as necessitated by Applicant’s arguments and amendments filed 06/15/2026.
Regarding independent claim 66 steps h and i, Fehlings teaches a method of making neural progenitor cells (spNPCs) having spinal identity comprising producing first caudalized NPCs which includes steps of passaging NPCs and incubating the NPCs in culture media supplemented with a RAR agonist such as Retinoic Acid (RA) to produce caudalized NPCs (Fig 1A and 10A, para. 0015, 0046).
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As seen in Figure 10D below, the caudalized cells express reduced levels of Otx2 levels compared to that of unpatterned NPCs, although posteriorized NPCs are not explicitly stated, these are viewed as an intermediary while the caudalized NPCs are produced from unpatterned NPCs exposed to retinoic acid to eventually produce caudalized NPCs in the same population (para. 0046).
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As retinoic acid (RA) is utilized in both the claimed invention and caudalization of Fehlings, the same method steps yield the same results. Therefore, the caudalized cells would express reduced levels of Otx2 levels compared to the posteriorized cells. Fehlings additionally teaches passaging the caudalized NPCs in suitable culture media supplemented with retinoic acid and an EGFR agonist (para. 0015, step g). Fehlings teaches ventralization after caudalization utilizing a suitable media and then culturing in the presence of a FGF agonist such as FGF2, EGFR, PDGFR agonist (para. 0015, steps h-I, para. 0064,). Fehlings discloses the use of 740 Y-P (PDGFR 740Y-P)” (para. 0070). The unpatterned NPCs are obtained from rosettes.
While Fehlings does not teach explicitly that the method is for producing spinal identity neural progenitor cells (spNPCs), the progenitor cells are made through the same methods steps as the invention, therefore, having the same properties.
Moreover, regarding step j, Fehlings teaches the addition of heparin and FGF after the NPCs are produced (Fig. 7). This reads on dual activation of PI 3-kinase-Akt pathway and FGF pathway, therefore, increasing the proliferation with a reasonable expectation of success.
Thus, Fehlings reads on step a (in part), step d (in part), step g (in part), step h, step i, and step j.
However, Fehlings does not teach in step a of culturing iPSCs (pluripotent stem cells), that TGFP inhibitor, FGF2 agonist, Wnt inhibitor, and BMP inhibitor are present in the media. TGFP inhibitor, FGF2 agonist, and BMP inhibitors are only in their induction media.
Ding teaches FGF-2 directly regulates activity to maintain ESC and iPS cells in an undifferentiated state (p. 422, 1st paragraph). Both Wnt inhibitor (DKK-1) and FGF-2 were cultured together and no significant change was found from regulating activity of TCF/LEF (p. 427, 1st paragraph).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date to put a BMP inhibitor, TGFP inhibitor, FGF2 agonist, and Wnt inhibitor in the media of step a) as some are known to be part of neural differentiation in figure 3 of Fehlings (See FGF, TGFbi, BMPi, Noggin) in addition to a Wnt inhibitor as taught by Ding with a reasonable expectation of success. An artisan would be motivated to do so as all of Fehlings inhibitors and FGF are applied to the media after the iPSC media in the method, therefore it would be obvious to one of ordinary skill in the art to apply the same inhibitors to the step previous in culturing iPSCs to the same end result of NPCs. Additionally, Ding teaches both Wnt inhibitor (DKK-1) and FGF-2 were cultured together regulating activity of TCF/LEF. Therefore, Wnt inhibitors and FGF-2 are known to work together to maintain iPSCs.
Regarding step b, as the combination of Fehlings and Ding teach iPSCs in a TGFP inhibitor, FGF2 agonist, Wnt inhibitor, and BMP inhibitor, this reads on a culture media containing Wnt inhibitor, and BMP inhibitor.
Regarding step c, Fehlings and Ding do not teach the formation of embryoid bodies (EBs) in serum free media.
Plaistead teaches a method wherein hiPSC form embryoid bodies (EBs) on the fifth day without FGF supplementation in the media which form rosette structures when supplemented with bmp inhibitors then cultured in the presence of FGF to obtain NPCs (p. 3, Derivation and maintenance). As seen in the method detailed, the human ESC medium is serum free (p. 3).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date to modify the teachings of Fehlings and Ding with the teachings of Plaistead to arrive at the claimed method involving steps in serum free media to achieve embryoid bodies with a reasonable expectation of success. An artisan would be utilizing a known technique to modify the method of producing NPCs from hiPSCs.
Regarding step d, the combination of Fehlings, Ding and Plaistead make obvious the formation of rosettes. Fehlings teaches rosettes are neural tube-like rosettes formed during the course of neural induction (p. 28, step 10). Therefore, neuroectodermal cells are present.
Regarding step e, the combination of Fehlings, Ding and Plaistead make obvious the formation of neuroectodermal cells from tube-like rosettes. However these references do not teach priming them to stay in the ectodermal cell fate expressing markers such as Pax6 and Sox1 by using EGF-L7 or its agonist.
Bicker teaches that the addition of EGFL7 pushes activated NSCs (neural stem cells) towards quiescence and neuronal progeny such as NPCs and activated NSCs towards differentiation through promoting the Notch signaling system (Abstract, p. 7, 2nd column).
It would have been obvious to the ordinary artisan, that the EGF-L7 of Bicker could have been applied to the method of Fehlings, to produce primed unpatterned NPCs from the unpatterned NPCs with a reasonable expectation of success. As Fehlings teaches a process of differentiation, an artisan would have been motivated to utilize a protein such as EGF-L7 known to induce differentiation and promote the Notch signaling system. As discussed above, as each and every method step is the same, the same results will occur such as posteriorized NPCs expressing higher levels of at least one Hox gene, expressing Pax6 and Sox1, and lower levels of at least one of the brain markers such as Gbx2, Otx2 and FoxG1 compared to unpatterned NPCs.
Regarding step f, the combination of Fehlings, Ding, Plaistead, and Bicker make obvious the primed cells of e). Moreover, Fehlings teaches that unpatterned NPCs are subjected to culture with one or more of FGFR agonists such as FGF2 and FGF8 (para. 0064, 0078). There is no definition for “high” as it is a relative term, therefore, it is interpreted that the exemplary concentrations of FGF agonists at 40ng/mL (p. 28, step 12). It would have been obvious to one of ordinary skill in the art at the time of the effective filing date to utilize both FGF2 and FGF8 in combination at those concentrations as they are both known FGF agonists utilized for the same purpose.
Regarding step g, the combination of Fehlings, Ding, Plaistead, and Bicker make obvious the cells of f). As discussed above, Fehlings teaches caudalization with RA. However, these references do not additionally teach a wnt agonist such as AZD2858, Wnt agonist 1, CP21R7 (CP21) or Wnt.
Bejoy teaches due to the neural patterning effect, Wnt signaling can efficiently promote motor neuron differentiation from hPSCs, in combination with caudalization factor retinoic acid (RA) and ventralization factor SHH. Wnt signaling may elevate the threshold level of SHH signaling to enrich motor neural progenitors. (p. 4, 1st column). Wnt activation induces a caudal fate of neural progenitors that more easily differentiate into motor neurons (p. 4, 1st column). Known wnt activators/agonists are canonical ligands such as wnt3a and gsk inhibitors such as CHIR99021 (Table 2). As evidenced by Fehlings, other known wnt agonists are wnt agonist 1.
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date to add wnt agonists such as wnt agonist 1 as taught by Bejoy and Fehlings at the time of introducing RA in Fehlings and Bicker with a reasonable expectation of success. An artisan would have been motivated to do so as the RA is being utilized to caudalize the NPCs in Fehlings and Bejoy teaches wnt activation induces caudal fate.
Regarding results such as marker expression, cell type induction and others, as each and every method step is made obvious, the same results would also occur with a reasonable expectation of success.
Regarding claim 67, Fehlings, Bicker, Plaistead, Ding and Bejoy make obvious the method of claim 66. Moreover, claim 67 is merely stating an inherent characteristic or intended use which does not provide further structure to 740Y-P or an active method step of claim 66.
Regarding claim 68, Fehlings, Bicker, Plaistead, Ding and Bejoy make obvious the method of claim 66. Thus, the culture composition utilized within 66 is also rendered obvious.
Regarding claim 69, Fehlings, Bicker, Plaistead, Ding and Bejoy make obvious the culture composition based on claim 68. Moreover, Fehlings teaches components of the compositions of Table 1 in the present application in their table on p. 39.
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It is interpreted that “base media” is the DMEM/F12 medium and DMEM/F12 medium supplemented with sodium pyruvate and Neurobasal Media components. As seen above DMEM/F12 medium supplemented with sodium pyruvate is taught by Fehlings. Moreover, for neuronal differentiation medium from EBs, Bicker utilizes Neurobasal medium (p. 3, last paragraph). Therefore, it would be obvious to combine the two different media which are utilized for the same purpose of neuronal differentiation and neural induction.
Regarding claim 70, Fehlings, Bicker, Plaistead, Ding and Bejoy make obvious the method of claim 66. Thus, the isolated population of spNPC of 66 is also rendered obvious..
Regarding claim 71, Fehlings, Bicker, Plaistead, Hung and Ding make obvious the method of claim 66, Fehlings teaches spinal cord injury treatment or demyelination disease (i.e. neurodegenerative) as uses for the isolated cells which would be administered to a subject (para. 0027, 00150-151).
Therefore, the invention would have been obvious to one of ordinary skill in the art.
In response to Applicant’s arguments and amendments filed 06/15/2026,
Applicant’s arguments and amendments have been considered regarding the 103 rejections, however they are not persuasive.
Applicant reiterates the arguments of the 102 above. Moreover, the limitations of utilizing EGFL7 to prime the cells are not taught by any of the secondary references. Applicant states that a skilled person would not be motivated to combine multiple references as the Office has to modify Fehlings.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, while EGFL7 is not a “conventional” culture component for neural patterning as disclosed by Applicant on p. 8 of the Remarks, as discussed above, Bicker teaches that the addition of EGFL7 pushes activated NSCs (neural stem cells) towards quiescence and neuronal progeny such as NPCs and activated NSCs towards differentiation through promoting the Notch signaling system (Abstract, p. 7, 2nd column). The rejection further states that motivation to utilize EGFL7 within a differentiation process is present as it is known that the protein EGFL7 is known to induce differentiation and promote the Notch signaling system. Thus, while it is not the same motivation of the present invention, there is still motivation present to utilize EGFL7 within the cell culture process which would lead to the same results.
In response to applicant's argument that the examiner has combined a large number of references, reliance on a large number of references in a rejection does not, without more, weigh against the obviousness of the claimed invention. See In re Gorman, 933 F.2d 982, 18 USPQ2d 1885 (Fed. Cir. 1991).
Applicant argues that the final step utilizing 740Y-P along with FGF2 and an EGFR agonist to stabilize spNPC identity has not been described in the manner utilized in the present application. Applicant further states that it results in NPCs with elevated Hox gene expression and downregulation of brain markers and that the stepwise application of the combinations influences the expression.
The Examiner states that Fehlings provides teachings of utilizing 740Y-P which reads on the present invention. If the markers are obtained specifically and solely by a specific order of components a Declaration can be provided to detail the evidence and the claims should reflect the exact parameters for how unexpected results may be obtained.
Applicant argues that the steps are a “defined, synergistic process which leads to a result that would not have been expected.”
The Examiner advises that, if unexpected results or synergy is found within the invention, Applicant should provide the evidence in a Declaration or point to where such results are found within the specification that would be considered synergistic or unexpected.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDRA CONNORS whose telephone number is (571)272-7010. The examiner can normally be reached Monday - Friday (9AM-5PM).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MARIA LEAVITT can be reached at (571) 272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ALEXANDRA F CONNORS/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
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