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 – 13 are pending. Claims 2 and 3 have been canceled.
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, 4 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Luo et al. (Culture of endodermal stem/progenitor cells of the mouse tongue, In Vitro Cell.Dev.Biol. – Animal (2009) 45:44 – 54; hereinafter Luo), in view of Mead et al. (US2022/0323406 A1; hereinafter Mead), Hiroo (JP2019165654), Kim et al. (KR20200138067; hereinafter Kim), Biggs et al. (Insulin-Like Growth Factors Are Expressed in the Taste System, but Do Not Maintain Adult Taste Buds, PLoS One. 2016 Feb 22;11(2); hereinafter Biggs), and Kuwahara et al. (Generation of a ciliary margin-like stem cell niche from self-organizing human retinal tissue. Nat Commun. 2015;6:6286. Published 2015 Feb 19; hereinafter Kuwahara).
Regarding claims 1, 4 and 5, Luo discloses in a study related to the culture of endodermal stem/progenitor cells of the mouse tongue, a technique that utilizes the anterior tongue of the mouse (p. 46, Cell isolation…, anterior region). Luo also discloses (p. 45, 1st para.) the pathways to target specialized cell types (i.e. Bmp, Shh, Notch, and Wnt) of the filiform and fungiform papillae. Luo further discloses that the cells of the anterior express ‘soft’ orthokeratins compared to ‘hard’ orthokeratins of the posterior due to a lack of keratohyalin in the posterior (1st page, Introduction). Keratohyalin is essential for maintaining a protective, hydrated epithelium that can support the development and maintenance of taste papillae.
Mead suggests that certain small molecule reprogramming agents (para. [0088]; a FGFR inhibitor, a GSK3 inhibitor, and a ROCK inhibitor) are employed in the differentiation of stem cells into “retinal” or “taste bud” epithelial organoids (paragraph [0076]). Mead further discloses contacting a population of cells with the Wnt agonist and GSK3 inhibitor, CHIR99021 (para. [0010]). Wnt signaling is essential for organoid engineering because it acts as the primary driver of stem cell self-renewal, proliferation, and niche maintenance in 3D culture systems. FGFR inhibitors enable the precise timing of signaling activation and inhibition to switch from expansion (stemness) to differentiation. The use and effect of Y-27632 (differentiation medium) permits the survival of dissociated stem cells and is removed during the induction phase of the culture.
Hiroo teaches a medium composition (p. 5, middle of page – Noggin (Bmp) and R-spondin (Wnt)) (p. 6, 1st full paragraph, y-27632) for inducing differentiation of taste bud cell organoids from HOPx-positive anterior tongue epithelial stem cells (p. 9, 1-3. Cell sorting) that comprises the components of claim 1 except for FGF2, IGF1 and SAG.
Kim discloses the use of a taste culture medium for differentiating epithelium cells of the circumvallate papillae (back of tongue) into organoids that includes a FGF and SAG (p. 6, 2nd para.). Furthermore, Biggs teaches that IGFs have (Abstract) a potential role in establishing the initial number of taste buds. Also, Biggs discloses that IGF interacts with Wnt, sonic hedgehog, and other factors that regulate taste bud development/maintenance (p. 10).
Kuwahara teaches the step-wise induction reversal method for the growth of de novo retinal tissue from epithelial progenitor cells, which uses Y-27632, CHIR99021, and SU5402 (Fig. 2a). Kuwahara goes on to disclose the addition of 3 µM of CHIR99021 and 5 µM of SU5402 for induction and cellular differentiation (p. 13, Kuwahara Induction-reversal culture).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the anterior tongue cells/pathway targeting/motivation/comparison of anterior and posterior tongue cells of Luo with the teachings/components of the medium of Hiroo in regard to culturing anterior epithelial cells with the added factors of Kim, in addition to Biggs’ motivation/suggestion on the use of IGF to induce taste bud organoid differentiation. It is also obvious to utilize the motivation/knowledge from Mead to treat the epithelial cells of the tongue with CHIR99021 and SU5402 at the concentrations suggested by Kuwahara in order to produce a taste bud organoid induction medium composition. Doing so would improve taste bud cellular differentiation according to Luo, Biggs, and Mead.
Response to Arguments
Claims 2 – 3 have been canceled.
Claim 1 was rejected under 35 U.S.C. 103 over Hiroo and claims 2 – 13 were rejected under 35 U.S.C. 103 over Hiroo, Kim, Biggs, Mead, and Kuwahara.
Applicant’s arguments, see remarks, p. 5, filed 07/01/2026, with respect to the rejection(s) of claim(s) 1 – 13 under 35 U.S.C. 103 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection under 35 U.S.C. 103 of claims 1 and 4 – 5 is made and modified in view of Luo, Mead, Hiroo, Kim, Biggs, and Kuwahara.
Applicant argues the cited references do not provide a proper motivation to combine their teachings, nor do they provide a reasonable expectation of success, posterior tongue-derived organoid culture conditions compared to anterior-derived, and that CHIR99021/SU5402-containing second differentiation medium is not a routine optimization.
The medium composition claims at present are directed to a generalized composition for generating organoids from epithelial cells derived from the tongue, thus the Examiner was able to search the prior art and find references directed to the limitations of the claims. Luo provides a framework of why anterior cells should be selected compared to posterior cells of the tongue; and the pathways to target for the developing filiform and fungiform papillae. Mead does suggest that epithelial organoids (such as taste bud and retinal) can be treated with an FGFR inhibitor, a GSK3 inhibitor, and a ROCK inhibitor. Thus, Kuwahara’s composition proves to be a nice starting point for epithelial cell-based organoids. Biggs disclosure that IGF interacts with Wnt, sonic hedgehog, and other factors that regulate taste bud development/maintenance made it obvious for adding to the protocol.
Applicant’s arguments, see p. 10, filed 07/01/2026, with respect to the rejection(s) of claim(s) 6 – 13 have been fully considered and are persuasive. The 35 U.S.C. 103 rejection of claims 6 – 13 has been withdrawn in view of Hisha et al. (Establishment of a Novel Lingual Organoid Culture System: Generation of Organoids Having Mature Keratinized Epithelium from Adult Epithelial Stem Cells. Sci. Rep. 3, 3224, 2013; hereinafter Hisha).
In regard to the method of producing taste bud organoids derived from the anterior tongue epithelium without a selection process using a marker, the Examiner found a reference, Hisha, in which cultured anterior (p. 2, Results, Organoid formation…) tongue epithelium cells without a selection marker were used to form organoids. Hisha reports no taste bud cells (p. 2, 2nd column, 2nd para.) expanded in their culture system. Therefore, the prior art does teach away from culturing anterior tongue epithelium without a selection marker for the purpose of inducing the differentiation of taste bud organoids.
"[W]hen the prior art teaches away from combining certain known elements, discovery of successful means of combining them is more likely to be nonobvious." KSR, 550 U.S. at 416, 82 USPQ2d at 1395.
Allowable Subject Matter
Claims 6 – 13 are allowed.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to WALTER JACKSON III whose telephone number is (571)272-0247. The examiner can normally be reached M-F 9:00A - 5:00P.
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/WALTER JACKSON III/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
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