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 .
Claim Status
Claims 1-3 and 7-20 are pending.
Claims 7-14 and 16-20 are withdrawn.
Claims 1-3 and 15 are under examination.
Maintained 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.
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.
Claims 1, 3 and 15 remains rejected under 35 U.S.C. 103 as being obvious over Gonzalez et al. (Molecular Psychiatry, 23(12), pp.2363-2374, 2018.; see IDS filed 21st, December, 2021; henceforth “Gonzalez”) in view of Qian et al. (Cell. 2016 May 19;165(5):1238-1254. Epub 2016 Apr 22.; henceforth “Qian”) and Watanabe et al. (Cell Rep. 2017 Oct 10;21(2):517-532.; henceforth “Watanabe”).
Regarding claim 1, Gonzalez discloses a production method for a cerebral organoid having amyloid plaques (Figure 3; see also “amyloid plaques and neurofibrillary tangles” abstract), the method comprising:
(a') culturing a pluripotent stem cell in a feeder-free manner (iPSCs are plated directly on concave plates without feeder cells; see “cells were plated in 96-well plates with a concave bottom” pg. 2365 col. 2 and this step is therefore in a “feeder-free manner” as claimed because there are no feeders present in this step) in the presence of 4 ng/mL FGF-2 (bFGF pg. 2365 col. 2 1st para; encompassed by the claimed “less than 100 ng/mL”) for 6 days (days 0 to 6; pg. 2365 col. 1-2 “Generation of cerebral organoids”);
wherein the pluripotent stem cell has a mutation in an Alzheimer's disease-related gene,
wherein the Alzheimer's disease-related gene is a presenilin 1 (PS1 gene)(“missense mutation (A246E) in the presenilin 1 (PSN1) gene linked to early-onset AD” pg. 2 col. 1);
(a) forming an embryoid body from the pluripotent stem cell after step (a') (“At day 6, the culture medium was replaced with neural induction medium” pg. 2365 col. 2)
(b) embedding the embryoid body after the (a) in an extracellular matrix and three-dimensionally culturing the embedded embryoid body (“COs were embedded in Geltrex LDEV-Free drops (Gibco) and cultured in ultra-low attachment six-well plates (16 COs/well) in differentiation medium” pg. 2365 col. 2) to form an organoid; and
(c) removing the organoid after the (b) and subjecting the removed organoid to stirring culture in a medium (“COs were transferred to differentiation medium” and “placed in an orbital shaker” pg. 2365 col. 2).
Regarding the culture length of claim 1 (a’), Applicant is directed to MPEP section 2144.05 which states 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) (Court held as proper a rejection of a claim directed to an alloy of "having 0.8% nickel, 0.3% molybdenum, up to 0.1% iron, balance titanium" as obvious over a reference disclosing alloys of 0.75% nickel, 0.25% molybdenum, balance titanium and 0.94% nickel, 0.31% molybdenum, balance titanium. "The proportions are so close that prima facie one skilled in the art would have expected them to have the same properties.").
Therefore, regarding the culture length of claim 1 (a’), because, as stated above, Gonzalez discloses a culture length of 6 days, which is so close to slightly above 7 days (such as 7 days and 1 minute which is encompassed by the claimed “more than one week”), that one of ordinary skill of the art would expect the culture lengths to have the same properties, the taught value of 6 days of Gonzalez makes the value of slightly above 7 days, which encompassed by instant claims, obvious.
Additionally, regarding claim 1 (a’), applicant is reminded that generally, differences in timings will not support patentability of subject matter encompassed by the prior art unless there is evidence indicating such timing is critical (MPEP 2144.05 II).
However, regarding claim 1 (a), although Gonzalez teaches a step of forming and embryoid body, Gonzalez is silent to the step including a SMAD inhibitor.
Nevertheless, regarding claim 1, Qian teaches a production method for a cerebral organoid comprising forming, in the presence of a SMAD inhibitor, an embryoid body from a pluripotent stem cell (“treated human iPSCs with dual SMAD inhibitors (dorsomorphin and A-83)” pg. 1239 col. 1 2nd para.) to pre-pattern embryoid bodies and to reduce tissue heterogeneity.
Therefore, regarding claim 1 (a), it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to practice the method of Gonzalez, and combine the known prior art element of the dual SMAD inhibitors (which include “a SMAD inhibitor” as claimed) during the embryoid body formation to obtain the predictable result of a pre-patterned embryoid body. One of ordinary skill would have been motivated to do so as taught by Qian to pre-pattern the embryoid bodies to the desired neural fate and to reduce tissue heterogeneity, (“pre-patterned embryoid bodies to the fate of a specific brain region” pg. 1239 col. 1 2nd para.). Regarding the reasonable expectation of success, Qian evidences forming, in the presence of a SMAD inhibitor, an embryoid body from a pluripotent stem cell (“treated human iPSCs with dual SMAD inhibitors (dorsomorphin and A-83)” pg. 1239 col. 1 2nd para.; see also Figure 1 and pg. 1252 col. 1-2 “Culture of Brain-Region-Specific Organoids”).
However, regarding claim 1 (b), although Gonzalez teaches three-dimensionally culturing the embedded embryoid body to form an cerebral organoid in a cerebral organoid differentiation medium, Gonzalez is silent to the presence of a SMAD inhibitor and a glycogen synthase kinase 3β (GSK3β) inhibitor during the culturing to form a cerebral organoid step (b).
Nevertheless, regarding claim 1 (b), Qian teaches embedding an embryoid body after forming, in the presence of a SMAD inhibitor, an embryoid body from the pluripotent stem cell (after “(a)”) in an extracellular matrix (Matrigel) and three-dimensionally culturing the embedded embryoid body in the presence of a SMAD inhibitor and a glycogen synthase kinase 3β (GSK3β) inhibitor to form an organoid (“treatment with three factors, GSK-3β inhibitor CHIR99021, recombinant WNT3A protein, and SMAD inhibitor SB-431542, during the Matrigel stage” pg. 1239 col. 2 3rd para.) to reduce cell death (“drastically reduced the number of CAS3+ cells at day 14” pg. 1239 col. 2 3rd para.).
Therefore, regarding claim 1 (b), it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to practice the method as suggested by Gonzalez in view of Qian, and combine the known prior art element of the treatment with three factors, GSK-3β inhibitor CHIR99021, recombinant WNT3A protein, and SMAD inhibitor SB-431542 (which includes the claimed “presence of a SMAD inhibitor and a glycogen synthase kinase 3β (GSK3β) inhibitor”) to obtain the predictable result of producing an organoid. One of ordinary skill would have been motivated to do so as taught by Qian to reduce cell death during the step of three-dimensionally culturing the embedded embryoid body (“drastically reduced the number of CAS3+ cells at day 14” pg. 1239 col. 2 3rd para.). Regarding the reasonable expectation of success, Qian evidences successfully culturing the embedded embryoid body in the presence of a SMAD inhibitor and a glycogen synthase kinase 3β (GSK3β) inhibitor to form an organoid during the embedded stage (“treatment with three factors, GSK-3β inhibitor CHIR99021, recombinant WNT3A protein, and SMAD inhibitor SB-431542, during the Matrigel stage” pg. 1239 col. 2 3rd para.).
However, regarding claim 1 (c), although Gonzalez teaches removing the organoid after embedding and culturing the embryoid body (the step “(b)” s claimed) and subjecting the removed organoid to stirring culture in a medium, Gonzalez, is silent to removing the organoid after the (b) from the extracellular matrix.
Nevertheless, regarding claim 1 (c), Qian teaches removing an organoid from extracellular matrix and subjecting the removed organoid to stirring culture in a medium (“followed by Matrigel removal and spinning” pg. 1239 col. 2 3rd para.; see also Figure 1B) to reliably generate organoids from multiple iPSC lines with reduced heterogeneity in organoid shape and size.
Therefore, regarding claim 1 (c), it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to practice the method as suggested by Gonzalez in view of Qian, and combine the known prior art element of removing the organoid from extracellular matrix before subjecting the removed organoid to stirring culture in a medium of Qian to obtain the predictable result of culturing an organoid. One of ordinary skill would have been motivated to do so as taught by Qian to reliably generate organoids from multiple iPSC lines with reduced heterogeneity in organoid shape and size (pg. 1239 col. 2 3rd para.; see also Figure 1B). Regarding the reasonable expectation of success, Qian evidences a step of removing an organoid from extracellular matrix and subjecting the removed organoid to stirring culture in a medium (“followed by Matrigel removal and spinning” pg. 1239 col. 2 3rd para.; see also Figure 1B).
However, regarding claim 1 (c), Gonzalez and Qian are silent to the presence of LIF.
Nevertheless, regarding claim 1, Watanabe teaches a production method for a cerebral organoid including culturing the organoid in a differentiation medium containing LIF (“addition of recombinant LIF to W5 organoids” pg. 6 4th para.; see also Figures 3A-3D) to make a cerebral organoid with enhanced production of basal radial glial (bRG) cells and formation of defined upper layers of neurons (pg. 7 1st para.).
Therefore, regarding claim 1, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to practice the method as suggested by Gonzalez in view of Qian and combine the known prior art element of addition of LIF to the differentiation medium to obtain the predictable result of making a cerebral organoid. One of ordinary skill would have been motivated to do so as taught by Watanabe to make a cerebral organoid with enhanced production of bRG cells and formation of defined upper layers of neurons (pg. 7 1st para.) and improved basement membrane at the outer margin (pg. 7 1st para.; Figure 3F). One would have also been motivated to do so as taught by Watanabe because the culture conditions including the LIF inhibitor decreased apoptotic death and were therefore conducive to long-term neuronal survival (pg. 7 1st para.; Figure 3G). Furthermore, Gonzalez specifically states a limitation of the organoid is that they “do not contain the same proportion of different type of nerve cells as the human brain” and have “a smaller proportion of glial cells and virtually no oligodendrocytes”(pg. 2371 col. 1 2nd para.) and therefore combing the LIF of Watanabe would improve the method as suggested by Gonzalez in view of Qian by increasing the amount of glial cells and improving the formation of defined upper layers of neurons (pg. 7 1st para.). Regarding the reasonable expectation of success, Watanabe evidences culturing an organoid in a differentiation medium containing LIF (“addition of recombinant LIF to W5 organoids” pg. 6 4th para.; see also Figures 3A-3D and pg. 7 1st para.).
Regarding the preamble of claim 1, the preamble merely states, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, and is not considered a limitation and is of no significance to claim construction (see MPEP 2111.02) See also Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997) ("where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation"). Additionally, as set forth above, Gonzalez in view of Qian and Watanabe suggest the limitations of all the active method steps of claim 1, and therefore the effect of the organoid “having amyloid plaques” would naturally follow the recitation of the taught steps. Lastly, the patient-derived iPSCs of Gonzalez taught above have a mutation of the missense mutation (A246E) in the presenilin 1 (PSN1) gene linked to early-onset AD (pg. 2 col. 1), which causes amyloid plaques to form, as evidence by Gonzalez (Figure 3; see also “amyloid plaques and neurofibrillary tangles” abstract), and therefore and organoid produced from iPSCS with this mutation would obviously comprise said amyloid plaques.
Regarding claim 3, further to the discussion of claim 1 above, Gonzalez teaches the cerebral organoids are cultured to 110 days in vitro (DIV) (pg. 2365 col. 2 2nd para.), which includes culturing for 100 or 101 days in the stirring culture medium ((110 days in vitro) –(5 days of neural induction medium) – (4 or 5 days differentiation in GelTrex) and results in the formation of amyloid plaques in the cerebral organoid (Figure 3; see also “amyloid plaques and neurofibrillary tangles” abstract).
Regarding claim 3, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). It is routine procedure to optimize component amounts to arrive at an optimal product that is superior for its intended use, since it has been held where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. See M.P.E.P. §2144.05. In the instant case, the taught values of culturing for 100 or 101 days in the stirring culture medium of Gonzalez lie within the claimed range and thereby make sit obvious.
Additionally, regarding claim 3, Applicant is reminded that generally, differences in timing will not support patentability of subject matter encompassed by the prior art unless there is evidence indicating such timing is critical (MPEP 2144.05 II).
Regarding claim 15, further to the discussion of claim 1 above, as stated above, Gonzalez discloses the Alzheimer's disease-related gene is the PS1 gene, and the mutation encodes an amino acid mutation of alanine to glutamic acid (A246E) at the 246th residue of the PS1 protein (pg. 4 col. 2 last para.).
Hence, the claimed invention as a whole was prima facie obvious.
Response to Arguments
Applicant’s arguments, filed 3rd, March, 2026 have been fully considered but are not found persuasive.
Applicant argues that the cited passage of Gonzalez does not correspond to part (a’) of claim 1 (pg. 6-7). Specifically, Applicant argues “In the section quoted above, Gonzalez teaches the use of ultra-low attachment concave bottom plates (96-well plate) as used for inducing differentiation of induced pluripotent stem (iPS) cells. These types of plates have a surface treatment which prevents cell adhesion. The iPS cells do not adhere, and iPS cells cannot be maintained and cultured on these types of plates. A person of ordinary skill in the art would appreciate that ultra-low attachment concave bottom plates as taught in Gonzales would not be suitable for the maintenance of undifferentiated iPSCs.
Typically, iPSC cells are kept adherent to a plate to control colony size and morphology and prevent
differentiation. Ultra-low attachment plates lack adhesive cues, which maintains iPSC pluripotency.” (pg. 7).
Applicant further argues “Consequently, Gonzales teaches culturing iPS cells in the presence of 4 mg/mL FGF2 after the initiation of differentiation induction, and Gonzales does not teach or suggest the claim element of "a feeder-free manner in the presence of less than 100 ng/mL of fibroblast growth factor- 2 (FGF2) for more than 1 week and equal to or less than 4 weeks", and a prima facie case of
obviousness has not been established for at least this reason. In contrast, as recited in part (a') of claim 1, the concentration of bFGF is reduced to 100 ng/mL or less during the phase of maintaining a pluripotent stem cell in an undifferentiated state, that is, before initiation of differentiation induction under feeder-free conditions.” (pg. 7-8).
Applicant further argues “in contrast, as recited in part (a') of claim 1, the concentration of bFGF is reduced to 100 ng/mL or less during the phase of maintaining a pluripotent stem cell in an undifferentiated state, that is, before initiation of differentiation induction under feeder-free conditions” (pg. 8)
In response, this is not found persuasive because Applicant is not appreciating the broadest reasonable interpretation of the claims. Step (a’) as presently claimed does not require conditions that maintain pluripotency and prevent differentiation and the present claims do not exclude initiation of differentiation induction during step (a’). It is noted that the features upon which applicant relies (i.e., “suitable for the maintenance of undifferentiated iPSCs” or “before initiation of differentiation induction”) are not recited in the rejected claim(s). 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). In other words, the “culturing iPS cells in the presence of 4 mg/mL FGF2 after the initiation of differentiation induction” (Applicants arguments pg. 7), falls under the broadest reasonable interpretation of instant claims.
Concerning the limitation of the range “for more than 1 week and equal to or less than 4 weeks,” state, that is, before initiation of differentiation induction under feeder-free conditions, as set forth above (see rejection of record above), Gonzalez discloses a culture length of 6 days, which is so close to slightly above 7 days (such as 7 days and 1 minute which is encompassed by the claimed “more than one week”), that one of ordinary skill of the art would expect the culture lengths to have the same properties, and therefore makes the claimed range obvious (see MPEP 2144.05 II).
Applicant argues “The pending claims therefore provide for an exceptional increase in the production efficiency of cerebral organoids” (pg. 8). Applicant argues Experimental Example 1 of the specification as filed describes preparation of a cerebral organoid, a scheme that is further exhibited in FIG. 1 as filed. The method outlined in the pending claims and further detailed in Experimental Example 1 provides an improved production efficiency of cerebral organoid formation “ (pg. 8 2nd para. to pg. 9 2nd para.).
In response, the alleged improved production efficiency is not a requirement of instant claims. As stated above, 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).
Further in response, Applicant has not specifically argued that the alleged improvements are unexpected results. For the sake of compact prosecution, the alleged improvements are considered as alleged unexpected results below.
In response to Applicant’s arguments, arguments of counsel cannot take the place of factually supported objective evidence in the record. See In re Schulze, 346 F.2d 500, 602, 145 USPQ 716, 718 (CCPA 1965), In re Huang, 100 F.3d 135, 139-40, 40 USPQ2d 1685, 1689 (Fed. Cir. 1996); In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984). Thus, Attorney statements regarding the unexpected result are not evidence without a supporting declaration. Specifically, Applicant has not provided objective scientific evidence on the record that increased production efficiency is facilitated over prior art methods.
Concerning the alleged unexpected results, the burden is on the Applicant to establish results are unexpected and significant (MPEP 716.02(b)(I)), Applicants have the burden of explaining the proferred data (and MPEP 716.02(b)(II)), and the objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support (MPEP 716.02(d)(I)).
The evidence relied upon should establish "that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance." Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992) (Mere conclusions in appellants’ brief that the claimed polymer had an unexpectedly increased impact strength "are not entitled to the weight of conclusions accompanying the evidence, either in the specification or in a declaration."); Ex parte C, 27 USPQ2d 1492 (Bd. Pat. App. & Inter. 1992) (Applicant alleged unexpected results with regard to the claimed soybean plant, however there was no basis for judging the practical significance of data with regard to maturity date, flowering date, flower color, or height of the plant.). See also In re Nolan, 553 F.2d 1261, 1267, 193 USPQ 641, 645 (CCPA 1977) and In re Eli Lilly, 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) as discussed in MPEP § 716.02(c) (MPEP 716.02(b)(I)). Evidence of unexpected properties may be in the form of a direct or indirect comparison of the claimed invention with the closest prior art which is commensurate in scope with the claims. See In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980) and MPEP § 716.02(d) - § 716.02(e). See In re Blondel, 499 F.2d 1311, 1317, 182 USPQ 294, 298 (CCPA 1974) and In re Fouche, 439 F.2d 1237, 1241-42, 169 USPQ 429, 433 (CCPA 1971) for examples of cases where indirect comparative testing was found sufficient to rebut a prima facie case of obviousness. (MPEP 716.02(b)(II)).
In the instant case, Applicant’s alleged unexpected results are insufficient to overcome the rejection of record under 35 U.S.C. 103 for several reasons.
First, as discussed above, the alleged unexpected results are not supported by factually objective evidence on the record.
Next, the data cited by Applicant (“This efficiency enhancement is further qualitatively observed in the contrast of FIG. 2A versus FIG. 2B” pg. 8) is a comparison of appears to be compared to a wildtype control and is not compared to the closest prior art. Because, the data cited by Applicant is not compared to the closest prior art, the statistical and practical significance of the date (required by MPEP 716.02(b)(II); see above) are not apparent.
Finally, the alleged unexpected results do not appear to be in scope with the claimed invention, as the cited results appear to correspond to the specific requirements of Experimental Example 1 (para. [0062-0071]).
Maintained Claim Rejections - 35 USC § 103
Claim 2 remains rejected under 35 U.S.C. 103 as being obvious over Gonzalez et al. (Molecular Psychiatry, 23(12), pp.2363-2374, 2018.; see IDS filed 21st, December, 2021; henceforth “Gonzalez”) in view of Qian et al. (Cell. 2016 May 19;165(5):1238-1254. Epub 2016 Apr 22.; henceforth “Qian”) and Watanabe et al. (Cell Rep. 2017 Oct 10;21(2):517-532.; henceforth “Watanabe”) as applied to claim 1 above, as evidenced by Lancaster et al. (Nat Protoc. 2014 Oct;9(10):2329-40.Epub 2014 Sep 4.; henceforth “Lancaster”) and Wenger et al. (Hypoxia (Auckl). 2015 Sep 18;3:35–43.; henceforth “Wenger”).
Regarding claim 2, further to the discussion of claim 1 above, Gonzalez, Qian and Watanabe are silent to oxygen concentrations during the stirring culture in a medium.
Nevertheless, regarding claim 2, Gonzalez cites Lancaster and states “Cerebral organoids (COs) were generated following the protocol described by Lancaster and Knoblich with minor modifications” (pg. 2365 col. 1 last para.).
Additionally, regarding claim 2, Lancaster evidences the stirring culture can be performed in “an orbital shaker installed in the incubator” (pg. 2337) and Lancaster evidences 5% CO2 conditions in the incubator (pg. 2332 col.1 and pg. 2334 2nd para.).
Moreover, regarding claim 2, Wenger evidences the oxygen concentration at 5% CO2 conditions in an incubator is 18.6% at sea level (pg. 36 col. 2 2nd para.; see also Figure 1).
Therefore, regarding claim 2, Lancaster evidences the orbital shaker as taught by Gonzalez would be present in 5% CO2 conditions, which would have 18.6% O2 as evidenced by Wenger above, in the incubator because Gonzalez cites Lancaster for protocol and Gonzalez does not indicate that the orbital shaker conditions are changed.
Regarding claim 2, as stated above, Lancaster and Wenger evidence the stirring culture is carried out in the presence of 18.6% O2. Instant claims recite “more than 20% by volume of oxygen” which includes all values more than 20% by volume of oxygen, including small incremental values only slightly above 20%, such as 20.1%. Applicant is directed to MPEP section 2144.05 which states 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) (Court held as proper a rejection of a claim directed to an alloy of "having 0.8% nickel, 0.3% molybdenum, up to 0.1% iron, balance titanium" as obvious over a reference disclosing alloys of 0.75% nickel, 0.25% molybdenum, balance titanium and 0.94% nickel, 0.31% molybdenum, balance titanium. "The proportions are so close that prima facie one skilled in the art would have expected them to have the same properties.").
Therefore, regarding claim 2, because the taught value of 18.6% O2 is so close to the claimed value of slightly more than 20%, such as 20.1% (encompassed by the instantly claimed “more than 20% by volume of oxygen”), that one of ordinary skill would have expected them to have the same properties, the taught value of 18.6% O2 makes the embodiment of slightly more than 20% of instant claims obvious.
Additionally, regarding claim 2, applicant is reminded that generally, differences in concentration will not support patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical (MPEP 2144.05 II).
Hence, the claimed invention as a whole was prima facie obvious.
Maintained Claim Rejections - 35 USC § 103
Claim 2 remains rejected under 35 U.S.C. 103 as being obvious over Gonzalez et al. (Molecular Psychiatry, 23(12), pp.2363-2374, 2018.; see IDS filed 21st, December, 2021; henceforth “Gonzalez”) in view of Qian et al. (Cell. 2016 May 19;165(5):1238-1254. Epub 2016 Apr 22.; henceforth “Qian”) and Watanabe et al. (Cell Rep. 2017 Oct 10;21(2):517-532.; henceforth “Watanabe”) as applied to claim 1 above, and in further view of Kadoshima et al. (Proc Natl Acad Sci U S A. 2013 Dec 10. Epub 2013 Nov 25.; henceforth “Kadoshima”).
Regarding claim 2, further to the discussion of claim 1 above, although Gonzalez teaches an orbital shaker, which is a suspension culture, Gonzalez, Qian and Watanabe are silent to oxygen concentrations during the stirring culture in a medium.
Nevertheless, regarding claim 2, Kadoshima teaches culturing to produce cerebral organoids under 40% O2 conditions during suspension culture (“cultured under 40% O2 conditions” pg. 20284 col. 2 2nd para.; see also pg. 20289; Materials and Methods “Long-Term Cortical NE Culture”) to allow robust growth of cortical tissue in long term suspension culture (pg. 20288 col. 1 1st para.).
Therefore, regarding claim 2, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to practice the method as suggested by Gonzalez in view of Qian, and combine the known prior art element of the 40% O2 conditions of Kadoshima, to obtain the predictable result of a suspension culture for making a cerebral organoid. One of ordinary skill would have been motivated to do so as taught by Kadoshima because the 40% O2 conditions allowed robust growth of cortical tissue in long term suspension culture (pg. 20288 col. 1 1st para.) and were suitable for culturing to produce cerebral organoids (pg. 20289; Materials and Methods “Long-Term Cortical NE Culture”). Regarding the reasonable expectation of success, Kadoshima evidences culturing to form a cerebral organoid under 40% O2 conditions (“cultured under 40% O2 conditions” pg. 20284 col. 2 2nd para.; see also pg. 20289; Materials and Methods “Long-Term Cortical NE Culture”)
Hence, the claimed invention as a whole was prima facie obvious.
Conclusion
THIS ACTION IS MADE FINAL. 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.
No claim is allowable.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIANA N EBBINGHAUS whose telephone number is (703)756-4548. The examiner can normally be reached M-F 9:30 AM to 5:30 PM ET.
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/BRIANA N EBBINGHAUS/Examiner, Art Unit 1632 /VALARIE E BERTOGLIO/Primary Examiner, Art Unit 1632
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