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. Restriction/Election Applicant’s election without traverse of Group I (Claims 1-4 and 13-16) in the reply filed on March 4, 2026 is acknowledged. Claims 5-12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected Group s II-III, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on March 4, 2026. Claim Objections Claims 4,15-16 are objected to because of the following informalities: “the retinal pigment epithelial cell” should be –the retinal pigment epithelial cells--. “A pluripotent stem cell” should be –pluripotent stem cells--. Appropriate correction is required. 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. 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. Claim s 1-4 and 13-16 are rejected under 35 U.S.C. 103 as being unpatentable over Tachibana (JP2018113945) in view of Reubinoff ( US 20180216064) . Tachibana teaches a string-like aggregate of stem cells such as pluripotent stem cells (ES and IPS cells are pluripotent) (Paragraphs 11-12,17 , 84-87 of Tachibana) . Paragraph s 93 -94 of Tachibana teach that such cells can further undergo differentiation as in instant Claims 1 , 4, 1 3 -16 . Tachibana teaches that stem cells in such spheroids/aggregates can differentiate into more mature cell types . However, Tachibana does not teach that pluripotent cells can be differentiated into retinal pigment epithelial cells. However, Reubinoff teaches that pluripotent stem cells in aggregate form can be differentiated into retinal pigment epithelia l cells (Paragraphs 67-69 of Reubinoff ) . It would have been obvious to an artisan of ordinary skill at the time of effective filing to have differentiated the pluripotent cells into retinal pigment epithelial cells. An artisan would have been motivated to have differentiated pluripotent stem cells into retinal pigment epithelial cells because retinal pigment epithelial cells “may serve as an in vitro model of retinal degeneration diseases, as a tool for high throughput screening for a therapeutic effect of small molecules, and for the discovery and testing of new drugs for retinal degeneration disease (Paragraph 5 of Reubinoff). Because Reubinoff teaches that that pluripotent stem cells can be successfully differentiated into retinal pigment epitheli al cells, there would be a high expectation for success.(Abstract of Reubinoff) as in instant Claims 1 , 4 ,1 3 -16. Dependent Claims taught by Tachibana The size /dimensions of such a sting-like aggregate will depend upon the amount of cells desired. MPEP § 2144.05 (II) states the following: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In reHoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc.v.Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In reKulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree “will not sustain a patent”); In re Williams, 36 F.2d 436, 438 (CCPA 1929) (“It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.”). See also KSR Int' l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying “the need for caution in granting a patent based on the combination of elements found in the prior art.”). A review of the specification fails to provide evidence that the claimed concentrations and aggregate size are critical. Absent such evidence , it would have been obvious to an artisan of ordinary skill at the time of effectively filing Tachibana to try a finite number of possible concentrations and aggregate sizes to predictably arrive at the desired concentration of cells and aggregate size through routine optimization. An artisan would have had a reasonable expectation of success in optimizing the concentrati on of cells and aggregate size because determining such parameters were long established in the art as demonstrated by Tachibana. Thus, Tachibana renders the instantly claimed dimensions above as in instant Claim 2 . Tachibana further teaches that the sting-like aggregates has a circular shape in the cross section ( Paragraph 84 -85 of Tachibana ) as in instant Claim 3 . Tachibana teaches a method of making a string aggregate of cells (pluripotent cells) and teaches that such cells can become further differentiated. Tachibana does not state specifically that such cells can further differentiate into retinal pigment epithelia l cells. However, an artisan would have been motivated to have differentiated such cells into retinal pigment epithelial cells since such cells can be used to successfully study disease and disorders associated with the eye as taught by Reubinoff . Given the teachings of the cited references and the level of skill of an ordinarily skilled artisan at the time of applicants’ invention, it must be considered, absent evidence to the contrary, tha t the ordinary skilled artisan would have had a reasonable expectation of success in practicing the claimed invention. All the claimed elements were known in the prior art, and one skilled in the art would have combined the elements as claimed by known methods with no change in their respective functions, and the combinations would have yielded predi ctable results to one of ordinary skill in the art at the time of the invention (See KSR Internation Co. v. Teleflex Inc. 82 USPQ2d 1385 (U.S. 2007). People of ordinary skill in the art will be highly educated individuals, possessing advanced degrees including M.D. and Ph.D.s. They will be medical doctors, scientists, or engineers. Thus, these people most likely will be knowledgeable and well-read in the relevant literature and have practical experience in wound care and biology. Therefore, the level of ordinary skill in this art is high. Conclusion All claims stand rejected. 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