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 .
DETAILED ACTION
Applicant’s arguments, filed 4/29/2026, have been fully considered but they are not deemed to be fully persuasive. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objects are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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.
Claims 1-9, 15- 17, and 139-142 are rejected under 35 U.S.C. 103 as being unpatentable over Sasaki (Transient FOXO1 inhibition in pancreatic endoderm promotes the generation of NGN3+ endocrine precursors from human iPSCs, Stem Cell Research, Volume 44, April 2020, 101754) in view of Ndlovu (Fibroblast Growth Factor 10 in Pancreas Development and Pancreatic Cancer. Front. Genet., 28 October 2018 Sec. Stem Cell Research Volume 9, 2018). Sasaki teaches an in vitro composition comprising a population of pancreatic progenitor cells and a medium comprising a Forkhead Box 01 (FoxO1) inhibitor and a notch signaling pathway inhibitor, wherein the population of pancreatic progenitor cells comprises cells that are PDXl-positive and NKX6. l-negative and cells that are PDXl-positive and NKX6 l-positive (abstract; Introduction) (present claim 1), the medium comprises a tpb (a PKC activator; there is no disclosed Wnt inhibitor in the medium) (Introduction; Section 3.2; Figure 2, A and E, (present claims 2 and 7), the notch signaling pathway inhibitor is a y-secretase inhibitor, wherein the Y-secretase may be DAPT (Section 2.8) (claims 3 and 4), the FOX01 inhibitor may be AS1842856 (Introduction), which corresponds to applicant’s
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(claim 5)
Wherein the FoxO1 inhibit is present in the medium at a concentration of 0.1-10 micromolar (Table 2) (claim 6), wherein the medium further comprises a fibroblast growth factor (Section 2.1), wherein approximately 50% (at least 50%) of the population of pancreatic progenitor cells are PDXl-positive and NKX6. l-negative, and/or no more than 50% of the population of pancreatic progenitor cells are PDXl-positive and NKX6. l-positive, and wherein no more than 50% of the population of pancreatic progenitor cells are PDXl-positive and NKX6. l-negative, and/or at least 50% of the population of pancreatic progenitor cells are PDXl-positive and NKX6.l-positive (Section 3.2), and wherein the medium further comprises a fibroblast growth factor (Section 2.1).
Sasaki fails to teach a fibroblast growth factor.
Ndlovu teaches that fibroblast growth factors interact with receptors (like FGFR2b) to stimulate the proliferation of epithelial progenitor cells and drive branching morphogenesis (Abstract; Fgf10 in Pancrease Development, Conclusion).
It would have been obvious to one of ordinary skill in the art at the time the invention was filed to add a fibroblast growth factor to the medium of Sasaki. The motivation for this would have been to stimulate the proliferation of epithelial progenitor cells and drive branching morphogenesis. Adding these keeps the progenitor cells in an actively dividing, unexpanded state without losing their foundational pancreatic identity.
Claims 1-17 and 139-143 are rejected under 35 U.S.C. 103 as being unpatentable over Sasaki (Transient FOXO1 inhibition in pancreatic endoderm promotes the generation of NGN3+ endocrine precursors from human iPSCs, Stem Cell Research, Volume 44, April 2020, 101754) in view of ) in view of Ndlovu (Fibroblast Growth Factor 10 in Pancreas Development and Pancreatic Cancer. Front. Genet., 28 October 2018 Sec. Stem Cell Research Volume 9, 2018) In further view of Abazari, PCL/PVA nanofibrous scaffold improve insulin-producing cells generation from human induced pluripotent stem cells, Gene 671, 2018, 50-57). The relevant portions of Sasaki and are given above.
Sasaki and Ndlovu fail to teach “wherein the medium further comprises a water-soluble synthetic polymer”
Abazari teaches that polyvinyl alcohol (a water-soluble synthetic polymer) is used in the context of pancreatic endocrine cells derived from human pluripotent stem cells (hPSCs) primarily as a biocompatible, hydrophilic scaffold material for 3D culture and as a protective, semipermeable barrier for transplantation (encapsulation), and improves cell-matrix interactions, supports the differentiation of hPSCs into functional pancreatic beta -cells, and helps maintain the structure of islet-like organoids, wherein the PVA is not hydrolyzed (wherein the PVA is at most 85% hydrolyzed) (Abstract; Introduction; Materials and Methods).
It would have been obvious to one of ordinary skill in the art at the time the invention was filed to incorporate polyvinyl alcohol into the composition of Sasaki. The motivation for this would be to provide a biocompatible, hydrophilic scaffold material for 3D culture and as a protective, semipermeable barrier for encapsulation. It would have been further obvious to optimize the w/v% of polyvinyl alcohol in the course of optimizing the composition for use in directing the differentiation of pancreatic progenitor cells into functional, insulin-producing pancreatic beta-cells, and in this way would find applicant’s presently claimed w/v range through routine experimentation. The prior art provides sufficient guidance to this end, as Abazari teaches 1.2 g of PVA polymer dissolved in 10 ml (Section 2.2), which is the equivalent of 0.12 w/v polyvinyl alcohol concentration, which reads on applicant’s 0.005% to 0.5% (w/v) (present claim 13).
Response to Arguments
Applicant’s arguments have been fully considered but are not found persuasive. Regarding applicant’s argument that the references cited in the previous office action fail to teach the new limitation “and one of a) a fibroblast growth factor, b) a Rho-associated, coiled-coil containing protein kinase (ROCK) inhibitor, or c) a transforming growth (TGF)-beta ligand,” the examiner’s response is that it would have been obvious to incorporate at least a fibroblast growth factor into the composition of Sasaki for the reasons set forth above.
Conclusion
Applicant’s amendent necessitated the new grounds of rejection. THIS ACTION IS THEFORE MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PAUL W DICKINSON whose telephone number is (571)270-3499. The examiner can normally be reached on M-F 9 AM to 7:30 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Hartley can be reached on 571-272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL W DICKINSON/Primary Examiner, Art Unit 1618
June 12, 2026
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