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, 41-43, 46-47, 49-50, and 52 are currently pending. Claims 1-39, 41-43, and 52 are withdrawn. Claims 46-47 and 49-50 are subject to this Office Action. This is the first Office Action on the merits of the claims.
Information Disclosure Statement
The references cited on the information disclosure statement(s) were considered and have been made of record.
Notably, one or more of the disclosure statements filed to date lists the following documents: International Search Report and PCT Written Opinion(s); Foreign Office Action(s).
The listing of the document(s) noted above is not considered to be an information disclosure statement (IDS) complying with 37 CFR 1.98. 37 CFR 1.98(a)(2) requires a legible copy of: (1) each foreign patent; (2) each publication or that portion which caused it to be listed; (3) for each cited pending U.S. application, the application specification including claims, and any drawing of the application, or that portion of the application which caused it to be listed including any claims directed to that portion, unless the cited pending U.S. application is stored in the Image File Wrapper (IFW) system; and (4) all other information, or that portion which caused it to be listed. In addition, each IDS must include a list of all patents, publications, applications, or other information submitted for consideration by the Office (see 37 CFR 1.98(a)(1) and (b)), and MPEP § 609.04(a), subsection I. states, "the list ... must be submitted on a separate paper." Therefore, the references cited in the document(s) noted above have not been considered.
Furthermore, the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Applicant is advised that the date of submission of any item of information or any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the IDS, including all "statement" requirements of 37 CFR 1.97(e). See MPEP § 609.05(a).
Note: If copies of the individual references cited on the document(s) noted above are also cited separately on the IDS (and these references have not been lined-through) they have been considered.
Claim Interpretation
The interpretation of the following terms, as set forth in the claims, is provided below.
The instant specification uses the phrase “conditionally expressed” synonymously with “transcribed and/or translated in” (see para. [0120] on p. 59).
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 46-47 and 49-50 are rejected under 35 U.S.C. 112(b) as failing to set forth the subject matter which the inventor or a joint inventor regards as the invention.
Claim 46, from which 47 and 49-50 depend, are indefinite in the recitation of the phrase "conditionally express…", without indicating the condition in which the proteins are expressed. Therefore, the scope of claims cannot be established.
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 and 49-50 is 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 claim 46).
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 and 49-50 are rejected under 35 U.S.C. 103 as being unpatentable over Han (supra) in view of Mousavinejad3 and Nistor4.
Regarding claim 47, 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.
Conclusion
Claims 46-47 and 49-50 are rejected.
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 - 6PM PT.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Janet Epps-Smith can be reached on (571) 272-0757. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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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; cited on the IDS filed 02/18/2022.
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.
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.