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 .
Election/Restrictions
Claims 1-22 are pending.
Applicant’s election without traverse of Group I, claims 1-16 in the reply filed on 08/31/2026 is acknowledged.
Claims 17-22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/31/2026.
Claims 1-16 have been examined on their merits.
Claim Objections
Claim 11 is objected to for the following informalities: the claim recites a redundant comma (“claim 9,,”).
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2, 4-9, and 14 are rejected under 35 U.S.C. 102(a)(1) or 35 U.S.C. 102(a)(2) as being anticipated by Nishida et al. (US20200010800A1, on IDS 09/30/2024).
Regarding claims 1 and 2, Nishida discloses methods for controlling differentiation of pluripotent stem cells (PSCs) towards neural crest cells (Abstract; paragraph [0013]; claims 13 and 14). It is noted that the instant specification broadly states, “The neural crest progenitor cell is a generic name of cell groups destined to differentiate into neural crest cell” (paragraph [0085]). Thus, the pluripotent stem cells as disclosed by Nishida are a type of neural crest progenitor cell.
Nishida discloses that the method comprises culturing PSCs on laminin (an ECM protein) (Abstract; paragraph [0013]; claims 13 and 14).
Regarding laminins and their naming conventions, in the art, laminins are named numerically by the composition of the α, β, and γ chains (e.g., α1, β1, γ1, etc.). It is noted that claim 1 does not require the laminin to have a specific γchain (and therefore, will be designated by “X” for the purpose of explanation).
Thus, claim 2 which is limited to “a laminin with its αchain being an α1 chain and its ßchain being a ß1 chain, a laminin with its αchain being an α2 chain and its ßchain being a ß1 chain, a laminin with its αchain being an α2 chain and its ßchain being a ß2 chain, and a laminin with its αchain being an α5 chain and its ßchain being a ß1 chain” refers to any of 1) α1ß1γX, 2) α2ß1γX, 3) α2ß2γX, or α5ß1γX laminin. To further simplify, in the art, these laminins are also referred to as 1) 11X, 2) 21X, 3) 22X, and 4) 51X, respectively. The simplified naming system will be used from here on.
See also as explained by Nishida, “laminin is a heterotrimeric molecule consisting of three subunits termed α, β and γ chains. Five kinds of a chains (α1 to α5), three kinds of β chains (β1 to β3) and three kinds of γ chains (γ1 to γ3) are known, and various combinations of these chains result in at least 12 kinds of laminin isoforms (see Table 1)” (paragraph [0043]).
Regarding laminins, in embodiments Nishida discloses differentiating neural crest cells on laminin 511 (paragraphs [0032-0033]; Figs. 17 and 18; i.e., “a laminin with its αchain being an α5 chain and its ßchain being a ß1 chain”).
In regards to “extracellular matrices comprising integrin-binding sites of these laminins”, it is noted that this refers to integrin binding sites on laminins themselves (see instant specification paragraph [0124]), “There is an integrin-binding site in laminin”).
In this regard, Nishida discloses that the laminin has integrin binding activity (paragraphs [0045-0047, 0052]).
Regarding claim 4, Nishida discloses that the integrin-binding site of the laminins comprises an E8 fragment of laminin (i.e., are an E8 fragment) (paragraphs [0045-0048, 0052]).
Regarding claim 5, Nishida discloses that after culturing cells express NGFR (i.e., p75) (paragraph [0091]; Fig. 10).
Regarding claim 6, Nishda discloses that culture surfaces are coated with laminin (i.e., the ECM) and that culturing is performed in a medium (paragraphs [0010 and 0054]).
Regarding claim 7, Nishida discloses that culturing is performed in a medium (paragraphs [0010 and 0054]). Since the result of culturing is differentiation of neural crest cells, it is suitable for maintaining those cells.
Regarding claim 8, Nishida discloses that neural crest cells differentiate (paragraphs [001, 0125]; Fig. 10) and therefore, are increased compared to the cell population before culturing.
Regarding claim 9, as above, Nishida discloses methods for controlling differentiation of pluripotent stem cells (PSCs) towards neural crest cells (Abstract; paragraph [0013]; claims 13 and 14), thus step (1). As above, regarding step (2), Nishida discloses that the method comprises culturing PSCs on laminin (an ECM protein) (Abstract; paragraph [0013]; claims 13 and 14). Additionally, in specific embodiments Nishida discloses differentiating neural crest cells on laminin 511 (paragraphs [0032-0033]; Figs. 17 and 18), which is noted stands for laminin with a α5 alpha chain, β1 beta chain, and γ1 gamma chain.
In regards to “extracellular matrices comprising integrin-binding sites of these laminins”, it is noted that this refers to integrin binding sites on laminins themselves (see instant specification paragraph [0124]), “There is an integrin-binding site in laminin”).
In this regard, Nishida discloses that the laminin has integrin binding activity (paragraphs [0045-0047, 0052]).
Regarding claim 14, Nishida discloses a timing of two weeks (paragraph [0124]), which overlaps with the claimed range of 7 to 18 days.
Therefore, Nishida anticipates the invention as claimed.
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.
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.
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 3 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Nishida et al. (US20200010800A1, on IDS 09/30/2024).
Nishida anticipates claims 1 and 9 as discussed above.
Regarding claim 3, while Nishida is silent as to a specific embodiment for culturing neural crest cells in laminin 221 (also referred to as α2β2γ1 or laminin-4), Nishida explicitly teaches that “laminin is a heterotrimeric molecule consisting of three subunits termed α, β and γ chains. Five kinds of a chains (α1 to α5), three kinds of β chains (β1 to β3) and three kinds of γ chains (γ1 to γ3) are known, and various combinations of these chains result in at least 12 kinds of laminin isoforms (see Table 1). The laminin used in the present invention may be any of these isoforms, and any appropriate laminin composed of a combination of an α chain selected from α1 to α5, a β chain selected from β1 to β3, a γ chains selected from γ1 to γ3 may be selected depending on the type of the desired differentiated cells” (paragraph [0043]; underlining added). Nishida also specifically identifies laminin 221 (21β2γ1, laminin 4) as one of the identified laminins that may be used (paragraph [0044]; Table 1, reproduced below) and teaches that it can bind to pluripotent stem cells (paragraph [0052]; Table 3).
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Therefore, it would have been prima facie obvious to select laminin 221 from the finite number of identified predictable solutions from the disclosure of Nishida.
Additionally, a person of ordinary skill in the art would have been motivated to select laminin, because Nishida teaches that laminin 221 has the same binding properties as laminin 211 which Nishida embodies as a substrate for differentiation of neural crest (claims 13 and 14). Furthermore, because Nishida explicitly states that “The laminin used in the present invention may be any of these isoforms” and identifies the species laminin 221 specifically, a person of ordinary skill in the art could have selected laminin 221 from the limited number of laminins with predictable results and a reasonable expectation of success.
Regarding claim 10, Nishida does not require steps of sorting or selecting neural crest cells with markers. Indeed, the methods of claims 13 and 14 of Nishida only require culturing PSCs on laminin which directs their differentiation to neural crest cells. Additionally, a person of ordinary skill in the art would have been motivated to forgo subjecting neural crest cells to further sorting or isolation in order to save time and reduce complexity. Therefore, it would have been predicably obvious to forgo a step of sorting or selecting neural crest cells with a neural crest marker.
Therefore, the teachings of Nishida render the invention unpatentable as claimed.
Claims 11-13 are rejected under 35 U.S.C. 103 as being unpatentable over Nishida et al. (US20200010800A1, on IDS 09/30/2024) in view of Pan et al. (Sciences Advances, 06/04/2021).
Nishida anticipates claims 1 and 9 as discussed above.
Regarding claims 11-13, Nishida teaches that the method can comprise culturing PSCs with a Wnt signaling activator (paragraph [0063]), including CHIR99021 (paragraph [0124]) which is a well-known GSK-3β inhibitor.
Nishida does not explicitly teach culturing PSCs with a SMAD inhibitor such as a TGFβ inhibitor.
However, a person of ordinary skill in the art would have been motivated to add a SMAD inhibitor, such as a TGFβ inhibitor because Pan teaches that TGFβ inhibitor SB431542 promotes (and in particular, in combination with CHIR99021) promotes reprogramming of cells to neural crest cells (Fig. 1, p2; p2, left column). Furthermore, because Pan demonstrates that TGFβ inhibitor SB431542 (and in combination with CHIR99021) can promote neural crest induction (Fig. 1, p2; p2, left column) a person of ordinary skill in the art could have modified the method of Nishida and also add a SMAD inhibitor, such as a TGFβ inhibitor, for the induction of neural crest cells with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Nishida and Pan render the invention unpatentable as claimed.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Nishida et al. (US20200010800A1, on IDS 09/30/2024) in view of Baba et al. (WO2020230832A1, on IDS 09/30/2024).
Nishida anticipates claims 1 and 9 as discussed above.
Regarding claim 15, Nishida teaches embodiments using serum replacement (paragraph [0054]) and therefore, does not “in a chemically defined medium without serum replacement or without serum” pe se.
However, methods for differentiating neural crest cells from pluripotent stem cells in chemically defined media lacking serum or serum replacement was known in in the art before the effective filing date, as taught by Baba. Specifically, Baba teaches that pluripotent stem cells were induced to differentiation to neural crest by being cultured in StemFit AK03N (Example, 1, page 10), which is a well-known chemically defined animal-origin free (thus, without serum or serum replacement) medium for culturing stem cells. A person of ordinary skill in the art would have been motivated to use a chemically defined medium that forgoes serum or serum replacement in order to avoid contamination with xenobiotic contaminants. Furthermore, because Baba teaches that neural crest cells can be cultured under these conditions, because commercial chemically defined media that forgoes serum or serum replacement is readily available (e.g., StemFit AK03N), and because in other embodiments Nishida uses StemFit media (paragraphs [0087, 0100], a person of ordinary skill in the art could have adapted the conditions of Nishida and performed the method in a chemically defined medium without serum replacement or without serum with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Nishida and Baba render the invention unpatentable as claimed.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Nishida et al. (US20200010800A1, on IDS 09/30/2024) in view of Toguchida et al. (WO2016104574A1, on IDS 03/31/2026).
Nishida anticipates claims 1 and 9 (thus, step (3)) as discussed above.
Regarding claim 16, regarding step (4), specifically, Nishda teaches that cells can be differentiated with factors including FGF2 (i.e., bFGF) (paragraph [0057]). While Nishida does not explicitly teach a step of culturing neural crest cells to mesenchymal stem cells, Toguchida teaches that neural crest cells can be further differentiated to mesenchymal stromal (stem) cells (MSCs) which are useful for testing against compounds (Abstract). Continuing, Toguchida teaches that this method comprises culturing induced neural crest cells to MSCs in media comprising FGF2 (i.e., bFGF) (paragraphs [0048, 0084], “Subsequently, differentiation induction from iNCC to mesenchymal stromal cells (MSC) was performed by . . . FGF2”). Therefore, it would have been predicably obvious perform a further step (4) and induce differentiation of MSCs in the presence of bFGF as claimed. A person of ordinary skill in the art would have been motivated to do so in order to test compounds against these cells as taught by Toguchida. Furthermore, because Nishida teaches that can be differentiated with factors including FGF2 (bGFG) and because Toguchida teaches that the differentiation step includes contacting cells with FGF2, it could have been done with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Nishida and Toguchida render the invention unpatentable as claimed.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH (PAUL) MIANO whose telephone number is (571)272-0341. The examiner can normally be reached Mon-Fri from 8:30am to 5:30pm.
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/JOSEPH PAUL MIANO/Examiner, Art Unit 1631
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