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 .
Restrictions/Elections
Applicant’s election of the following invention/species without traverse, as set forth in the Reply filed 10 October 2025, is acknowledged:
Applicant elects Group II.
Status of the Claims
Claims 1-39, 46-47, 49-50, and 85-92 are currently pending. Claims 1-39 and 89-91 are withdrawn. Claims 46-47, 49-50, 85-88 and 92 are the subject of this Office Action.
Withdrawn Claim Rejections
The previous rejections under 35 U.S.C. 112(b) are hereby withdrawn.
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.
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.
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.
Claim 46, 49-50, 85-88, and 92 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Han1.
Regarding claim 46, Han teaches hypoimmunogenic human pluripotent stem cells as well as methods for obtaining the same, wherein the cells have MHC class I and class II genes deleted, and wherein immune check point proteins, PD-L1 and CD47, are knocked in2 (reads on instant claims 46, 49-50, 85-88). Han further teaches induction of HLA-DR expression upon IFNγ stimulation was abolished in the hPSC-derived endothelial cells (see Han, e.g., at p. 10442 col. 1 and Fig. 1E; reads on instant claim 92).
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 46, 47, 49-50, 85-88 and 92 are rejected under 35 U.S.C. 103 as being unpatentable over Han (supra) in view of Mousavinejad3 and Nistor4.
The teachings of Han are discussed above and are incorporated herein.
The prior art of Han differs from the instantly claimed invention as follows: Han does not teach wherein the modified cells of the cell preparation are terminally differentiated cells.
Mousavinejad highlights the risk of tumorigenesis both immediately and long-term after stem cell transplantation (see Mousavinejad, entire document, e.g., at the abstract, p. 282).
Nistor teaches the terminal differentiation of human embryonic stem cell (hESC)-derived oligodendrocytes and administering the cells into mice (see Nistor, e.g., at col. 2 of p. 390, discussion, and Fig. 3 and 5).
Obviousness Analysis: In light of these teachings, 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 arrived at the presently claimed invention in view of the prior art because it amounts to no more than: the simple substitution of one known element for another to obtain predictable results, namely, the substitution of cell types (e.g., the terminally differentiated cell, e.g. oligodendrocyte, of Nistor for the stem cell of Han) to obtain the predictable results. Furthermore, a skilled artisan would have been motivated to use terminally differentiated cells instead of pluripotent stem cells, as pluripotent stem cells are known in the art to have high risk of tumorigenesis, as taught by Mousavinejad. See (MPEP 2143(I)(B), (G)).
Additionally, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Thus, a skilled artisan could predictably and reasonably arrive at the claimed polypeptide and methods of the instant application. See (MPEP 2143(I)(D)).
Accordingly, claims 46, 47 and 49-50 are rejected.
Response to Arguments
Applicant's arguments filed 06 April 2026 have been fully considered.
New claims 85-88 and 92, pertaining to the election of Group II without traverse, set forth in the Reply filed 10 October 2025, are examined on the merits.
Applicant's arguments regarding previous claim rejections under 35 U.S.C. 112 have been fully considered and are persuasive. Therefore, the previous claim rejections under 35 U.S.C. 112 are withdrawn.
Applicant's arguments regarding previous claim rejections under 35 U.S.C. 102 and 103 have been fully considered, but they are not persuasive. Applicable arguments pertaining to the rejections are addressed below.
Regarding the claim rejections under 35 U.S.C. 102 and 103, Applicant argues that Han only teaches constitutive expression of PD-L1, HLA-G, and CD47 while the present claims are directed to “cells of the preparation are modified to express, upon differentiation” (see Reply, p. 9). However, Applicant’s amendment merely requires upregulation of immune checkpoint proteins and decreased HLA expression upon differentiation, i.e., the final product having these features. The claims as written do not explicitly require that the starter cells do not demonstrate upregulation of immune checkpoint proteins and decreased HLA expression. Even if such a limitation was introduced into the claims, claims 46-47, 49-50, 85-88 and 92 are product by process claims. MPEP 2113 states that:
“[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985)
The product in claims 46-47, 49-50, 85-88 and 92 are a preparation of cells, and would still be anticipated/rendered obvious by Han in view of Mousavinejad and Nistor because the process steps do not render the preparation of cells distinct from the prior art preparation of cells.
Thus, the previous claim rejections under 35 U.S.C. 102 and 103 are maintained.
Conclusion
Claims 46-47, 49-50, 85-88 and 92 are rejected.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LEA S O'BRIEN whose telephone number is (703)756-4793. The examiner can normally be reached Monday - Thursday 9:00AM - 6:30PM PT.
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/LEA S O'BRIEN/Examiner, Art Unit 1646
/MARK HALVORSON/Primary Examiner, Art Unit 1646
1 XIAO HAN ET AL: "Generation of hypoimmunogenic human pluripotent stem cells", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, vol. 116, no. 21, 30 April 2019 (2019-04-30), pages 10441 - 10446, XP055640699, ISSN: 0027-8424, DOI: 10.1073/pnas.1902566116; art of record.
2 See Han. E.g., at the abstract, col. 2 of p. 10444- “In this study, we applied multiplex CRISPR/Cas9 genome editing to render hPSC hypoimmunogenic to both adaptive and innate immune responses. We specifically deleted the highly polymorphic HLA-A/-B/-C genes and prevented the expression of HLA class II genes by targeting CIITA. In addition, we introduced the immunomodulatory factors PD-L 1, HLA-G, and CD47 into the AAVS1 safe harbor locus. We found that engineered hPSC derivatives elicited significantly less immune activation and killing by T cells and NK cells and displayed minimal engulfment by macrophages.”
3 Mousavinejad et al. “Current Biosafety Considerations in Stem Cell Therapy”. Cell J. 2016 Jul-Sep;18(2):281-7. doi: 10.22074/cellj.2016.4324. Epub 2016 May 30. PMID: 27540533; PMCID: PMC4988427; art of record
4 Nistor et al. “Human embryonic stem cells differentiate into oligodendrocytes in high purity and myelinate after spinal cord transplantation”. Glia. 2005 Feb;49(3):385-96. doi: 10.1002/glia.20127. PMID: 15538751; art of record
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