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 .
Election/Restrictions
This action is in response to the papers filed on 01/26/2026. Claims 1-81 are currently pending as per claims filed on 01/26/2026.
Claims 2-7, 9, 11-13, 15, 17-22, 24, 28-35, 37, 39-47, 50, 52, 54-57, 59-67, 69-71, 73, 77, and 80 have been amended and claims 23-27, 29-55, 57-76 and 80-81 have been withdrawn by Applicants’ amendment filed on 01/26/2026. No claims were canceled or added.
Applicant’s election without traverse of Group 1, claims 1-22, 29, 77-79 in the reply filed on 01/26/2026 is acknowledged.
Applicant’s further election without traverse of the following species is acknowledged:
Species 1:
an amino acid sequence of the disrupted B2M gene as set forth in SEQ ID NO: 12 (Claim 3);
the target nucleotide sequence as set forth in SEQ NO: 17 (within SEQ ID NO:1) to which a gRNA binds (Claim 18);
and the gRNA sequence as set forth in SEQ ID NO: 18 (Claims 19-22)
Species 2:
MAD7 (Claims 13 and 16)
Examination will be limited to claims directed to the elected species, which are presently claims 1-13, 16-22, and 77-79, to the extent that they are readable on the elected embodiment.
Claims 14-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim.
Claim 23-28, 30-76 and 80-81 are withdrawn from further consideration by Applicants pursuant to 37 CFR 1.142(b), as being drawn to a nonelected subject invention, there being no allowable generic or linking claim.
Claim 29 is withdrawn from consideration by the examiner as being dependent on withdrawn claim 23.
. Applicant timely traversed the restriction (election) requirement in the reply filed on 01/26/2026.
The requirement is still deemed proper and is therefore made FINAL.
Therefore, claims 1-13, 16-22, and 77-79 are subject to examination to which the following grounds of rejection are applicable.
Claim Objections
The amendment to the claims filed on 01/26/2026 does not comply with the requirements of 37 CFR 1.121(c) because changes in claims 28 and 56 are not completely marked with the proper claim identifier. Amendments to the claims filed on or after 01/26/2026 must comply with 37 CFR 1.121(c) which states:
(c) Claims. Amendments to a claim must be made by rewriting the entire claim with all changes (e.g., additions and deletions) as indicated in this subsection, except when the claim is being canceled. Each amendment document that includes a change to an existing claim, cancellation of an existing claim or addition of a new claim, must include a complete listing of all claims ever presented, including the text of all pending and withdrawn claims, in the application. The claim listing, including the text of the claims, in the amendment document will serve to replace all prior versions of the claims, in the application. In the claim listing, the status of every claim must be indicated after its claim number by using one of the following identifiers in a parenthetical expression: (Original), (Currently amended), (Canceled), (Withdrawn), (Previously presented), (New), and (Not entered).
Any further claim amendments must comply with 37 CFR 1.121(c) or they may not be entered.
Priority
The instant application claims domestic benefit to US provisional patent
application number 63/357,922 filed on 07/21/2022. Thus, the earliest possible priority
for the instant application is 07/21/2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/14/2024 is not in
compliance with the provisions of 37 CFR 1.97. The following references have not been
considered by the examiner, as indicated on Form PTO 1449.
a) Reference “Universal donor cell-related plasmid B2M-CAGGS-HLA-E DNA SEQ ID 34” not been considered as it has not been provided in the application.
b) Reference “Universal donor cell-related plasmid B2M-CAGGS-PDL1 DNA DNA SEQ ID 34” not been considered as it has not been provided in the application.
c) Reference “Human B2M gene left homology arm (LHA-B2M) DNA SEQ ID 13” not been considered as it has not been provided in the application.
d) Reference “Sequence 19 from Patent US 10865424” not been considered as it has not been provided in the application.
e) Reference “Human beta-2-microglobulin (B214) gene fragment SEQ ID 6” not been considered as it has not been provided in the application.
f) Reference “Human B2M gene right homology arm (RHA-B2M) DNA SEQ ID 19” not been considered as it has not been provided in the application.
All other documents in said Information Disclosure statement were considered as
noted by the Examiner initials in the copy attached hereto.
Claim Interpretation
The term "payload" used in claim 78 is not specifically defined in the specification and there is no established meaning in the art. It is interpreted that any single amino acid, any single nucleotide, any polynucleotide, or any polypeptide may be a “payload”.
Claim Objections
Claim 9 is objected to because abbreviations such as HLA should be spelled out at the first encounter in the claims. Appropriate correction is required.
Claim 77 is objected to because abbreviations such as TCR should be spelled out at the first encounter in the claims. Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-13, 16-22, and 77-79 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
Claims 1-13, 16-22, and 77-79 are drawn to a population of induced pluripotent stem cells (iPSCs) comprising a disrupted beta-2-microglobulin (B2M) gene,
None of the subject matter of claims 1-13, 16-22, and 77-79 is necessarily isolated.
Given the disclosure it is evident that the claimed iPSCs comprising targeted insertion of a CAR transgene into B2M in human γδT cell-derived iPSCs is intended for use in immunotherapy to reduce the likelihood or degree of innate immune response in a human patient by a process that comprises administering iPSCs to a patient (e.g., paragraphs [0066], [0113], [0125] [0144] of the corresponding published application).
Once administered to a human patient, the engineered iPSCs, as well as the nucleic acid molecules (vectors) encoding the chimeric antigen receptor (CAR) that is expressed by the iPSCs become integral parts of a living human being. Accordingly, the claims, construed in this manner, are directed to non-patentable subject matter, namely a human being. Inasmuch as the claims may be broadly but reasonably construed as encompassing a living human, Applicant is duly reminded that Section 33(a) of the America Invents Act reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
Accordingly, claims 1-13, 16-22, and 77-79 are also rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. 101). See M.P.E.P. § 2105, which states:
If the broadest reasonable interpretation of the claimed invention as a whole encompasses a human being, then a rejection under 35 U.S.C. 101 must be made indicating that the claimed invention is directed to nonstatutory subject matter.
It is suggested that this issue may best be remedied by amending the claims to recite the limitation, “isolated” before “population”. See 1077 O.G. 24, April 21, 1987.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 5, 6, 9, and 77 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 5, 6, and 77 recites the limitation "the disruption comprises" in line 17 and 19, respectively. There is insufficient antecedent basis for the recitation of “the disruption” in the claim. Appropriate correction is requested.
Claim 9 and 10 recites the term “and/or” in line 7, and 10 and 12, respectively. It is unclear what the metes and bounds of this term, as “and” could be interpreted to include only HLA-A expression, only HLA-B expression, only HLA-C expression or HLA-A, HLA-B, and HLA-C expression, or, “or” would imply that the expression types are in the alternative. Appropriate correction is required.
Claim Interpretation
The phrase “gRNA binds to at least a portion of a complement sequence of” and “gRNA binds to a complement sequence of” recited in claim 17 and 18, respectively, are interpreted to mean that the gRNA binds to the complementary sequence of the respective SEQ ID NO, hence would be identical in sequence to the respective SEQ ID NO.
The phrase “gRNA comprises a sequence of” and “gRNA consists of a sequence of” in claims 19 and 20, respectively, are interpreted to mean that the gRNA can encompass a sequence within SEQ ID NO: 18, either in its entirety or partially.
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.
Claim(s) 1-13, 16-22, 77-79 are rejected under 35 U.S.C. 103 as being unpatentable over Izhar et al (US Patent Application No: US 20240042025 A1), and further in view of Watanabe et al (Stem Cells and Translational Medicine, 2017, pages 34-44), Das et al (US Patent Application No: US 20230248825 A1), Pulé et al (US Patent Application No: US 20200255494 A1), Lee et al (US Patent Application No: US 20220175839 A1), Fry et al (WO Publication No: WO/2023/183313 – too large to attach to file wrapper), Ando et al (US Patent Application No: US 20220339194 A1), Barghetti (US Patent Application No: US 20230235362 A1), and Donohoue (US Patent Application No: US 20250027078 A1) as evidenced by Wikipedia Beta-2 Microglobulinpp. (pp1-6 downloaded March 13, 2026).
Regarding claim 1, Izhar teaches knocking out (i.e. disrupting) the B2M gene in cells (para 0005) and “wherein the cell is a lymphocyte, a T cell, a T regulatory cell, a B cell, a natural killer (NK) cell, a macrophage, a stem cell, or a fibroblast, blood cell, hepatocyte, keratinocyte, or any other cell type capable of being reprogrammed to an induced pluripotent stem cell (iPSC)” (claim 25) and inactivating a B2M allele in a cell and “in some embodiments, the cell is an iPSC” (para 0013).
However, Izhar does not teach that the cells are iPSCs which have been generated by reprogramming γδ T cells.
Watanabe teaches a method of generating iPSCs from γδ T cells using the Yamanaka factors OCT4, SOX2, KLF4, and c-MYC (page 35, right col, Generation of iPSCs from Human γδ T Cell Culture, para 1) and they can provide a therapeutic cell source for novel adoptive cell therapies (page 35, left col, para 3).
It would have been prima facie obvious to one of ordinary skill, in the art at the time of the effective filing date, to modify the teachings of disrupting the B2M gene in cells such as T cells from Izhar with the teachings of reprogramming γδ T cells to become iPSCs from Watanabe to generate a population of iPSCs with a disrupted B2M gene. One would be motivated to do so since iPSCs are self-renewing and therefore one would have a regenerative cell source/consistent supply of cells to use for B2M gene disruption and, subsequently, use as a cell therapy source. As reprogramming cells into iPSCs and gene editing iPSCs are known techniques in the art, one would have a reasonable expectation of success.
Regarding claim 2, the teachings of Izhar and Watanabe render obvious claim 1.
However, Izhar and Watanabe do not teach wherein the disrupted B2M gene comprises a deletion of at least a portion of the nucleotide sequence of SEQ ID NO: 1 or of about or at least about 5-100% of the nucleotide sequence of SEQ ID NO: 1.
Das teaches a nucleotide sequence of SEQ ID NO: 48 identifying the B2M gene. When comparing the nucleotide of SEQ ID NO: 48 with the claimed nucleotide of SEQ ID NO:1 or a mutated form with a deletion of at least a portion of the sequence set forth in SEQ ID NO: 1 as recited in claim 2, a portion of the instant SEQ ID NO:1 is identical the nucleotide of SEQ ID NO: 48.
See sequence alignment below – shown are only positions 1-179 of SEQ ID NO: 48. Red box = SEQ ID NO:1; Green Box = reference application SEQ ID NO: 48; Yellow box = deletion in reference application SEQ ID NO: 48.
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Regarding claim 3, the teachings of Izhar and Watanabe render obvious claim 1.
However, Izhar and Watanabe do not teach wherein the nucleotide sequence of the B2M gene encodes an amino acid sequence that is about, at least about, or at most about 5-100% identical to SEQ ID NO: 12.
Pulé teaches an amino acid sequence of SEQ ID NO: 3 identifying the B2M amino acid sequence. When comparing the amino acid of SEQ ID NO: 3 with the claimed amino acid of SEQ ID NO: 12 as recited in claim 3, the instant SEQ ID NO:12 is identical the amino acid of SEQ ID NO: 3.
See sequence alignment below Red box = SEQ ID NO:12; Green Box = reference application SEQ ID NO: 3.
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Regarding claim 4, the teachings of Izhar and Watanabe anticipate claim 1.
Moreover, Izhar teaches that, using FACS analysis, 80% of gene edited cells are negative for B2M (as shown in Figure 4; in para 0164), rendering obvious the population of iPSCs of claim 1, wherein about 80% of the iPSCs do not express a detectable level of B2M.
Regarding claim 5 and 6, the teachings of Izhar and Watanabe anticipate claim 1.
Moreover, Izhar teaches “wherein alleles of the B2M gene in the cell are subjected to an insertion or deletion mutation” (claim 6), rendering obvious wherein the disruption comprises a deletion (claim 5 of instant application) or insertion (claim 6 of instant application) of at least one nucleotide base pair.
Regarding claim 7 and 8, the teachings of Izhar and Watanabe anticipate claim 1.
Moreover, Izhar teaches using FACS analysis, 80% of gene edited cells (are negative for B2M and the expression is reduced compared to a negative control cell with no B2M disruption (as shown in Figure 4; in para 0164), rendering obvious wherein the disrupted B2M gene exhibits reduced B2M expression relative to an undisrupted B2M gene (claim 7 of instant application) and wherein the reduced expression of B2M is reduced by about or at least about 5-100% as compared to the expression of B2M in a reference iPSC (claim 8 of instant application).
Regarding claim 9, the teachings of Izhar and Watanabe render obvious claim 1.
However, Izhar and Watanabe do not teach wherein the iPSCs comprising a disrupted B2M gene exhibit reduced expression of HLA-A, HLA-B, and/or HLA-C as compared to the expression of HLA-A, HLA-B, and/or HLA-C in a reference iPSC.
Lee teaches “repressing a B2M gene to produce HLA class I null T cell or stem cell for example a cell that does not express one or more HLA receptors on its surface” (para 0017). Furthermore, Lee teaches “the cells with modulated B2M expression lack significant class I HLA on their cell surface” and “the B2M-gene modified cells are further modified at the HLA-A, -B, -C genes” (para 0019). Finally, Lee teaches that gene modified cells for B2M show 92% knockout of HLA signal and it is relative to no Zinc finger nuclease (ZFM) control cells (i.e reference cells) (as shown in Figure 4A-E.). The examiner notes that MHC class I molecules are heterodimers that consist of two polypeptide chains, α and β2-microglobulin (B2M) as evidenced by Wkipedia.
In light of the teachings of Lee, it is noted that the claim is directed to an inherent result based on reduction of B2M expression leading to reduction in HLA expression. It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph). It is noted that, if the prior art discloses identical chemical structure, the properties applicant discloses and/or claims are necessarily present, In re Spada, 911 F.2d 705, 709, 15 USPQ2d. As such the functional limitations would be present in the identical compounds taught by Lee would therefore exhibit the phenotype of reduced expression of HLA-A, HLA-B, and/or HLA-C.
Regarding claim 10, the teachings of Izhar, Watanabe, and Lee render obvious claim 1 and 9. Moreover, Lee teaches that gene modified cells for B2M show 92% knockout of HLA signal and it is relative to no Zinc finger nuclease (ZFM) control cells (i.e reference cells) (as shown in Figure 4A-E), rendering obvious wherein the reduced expression of HLA- A, HLA-B, and/or HLA-C is reduced by about or at least about 5-100% as compared to the expression of HLA-A, HLA-B, and/or HLA-C in a reference iPSC.
Regarding claim 11, the teachings of Izhar and Watanabe render obvious claim 1, 7, and 8. Moreover, Izhar teaches a reference population of cells that are negative control cells with no nuclease and no guide sequence for B2M disruption (Table 7, Example 5), rendering obvious wherein the reference iPSC is a population of iPSCs in which B2M gene is not disrupted.
Regarding claim 12, the teachings of Izhar and Watanabe render obvious claim 1. Moreover, Izhar teaches a guide RNA (gRNA), used for targeting and knocking-out of the B2M gene by electroporating into primary T cells (para 0145) and Cpf1 which is an RNA-guided endonuclease (para 0128), rendering obvious wherein the disrupted B2M gene is generated by contacting the population of iPSCs with an RNA-guided endonuclease or a nucleic acid encoding the RNA-guided endonuclease and a guide RNA (gRNA), and wherein the gRNA binds to a target motif of a B2M gene.
Regarding claim 13 and 16, the teachings of Izhar and Watanabe render obvious claim 1 and 12.
However, Izhar and Watanabe do not teach wherein the RNA-guided endonuclease is MAD7.
Fry teaches inserting transgenes into endogenous gene loci such as B2M (abstract) of cells that can be iPSCs (page 2, para 0005) and the transgene insertion is carried out using a site-direct nuclease (i.e. RNA-guided endonuclease) such as MAD7 (page 5, para 0013).
It would have been prima facie obvious to one of ordinary skill, in the art at the time of the effective filing date, to modify the teachings of disrupting a B2M gene in iPSCs using a gRNA that targets a B2M gene from Izhar and Watanabe with the teachings of using MAD7 as the RNA-guided endonuclease for B2M gene disruption from Fry to generate a functional gene-editing system for disrupting the B2M gene. One would be motivated to do so to have multiple options of RNA-guided endonucleases when performing gene editing in cells. Since MAD7 can be used as an RNA guided endonuclease for B2M gene editing, as shown in Fry, one would have a reasonable expectation of success.
Regarding claim 17, the teachings of Izhar and Watanabe render obvious claim 1 and 12.
However, Izhar and Watanabe do not teach wherein the gRNA binds to at least a portion of a complement sequence of SEQ ID NO: 1.
Ando teaches gRNAs comprising a targeting sequence against the B2M gene (para 0468). More specifically, Ando teaches a targeting sequence of SEQ ID NO: 8661. When comparing the nucleotide sequence of SEQ ID: 8661 with the claimed nucleotide of SEQ ID NO: 1 as recited in claim 17, the instant SEQ ID NO: 1 is 100% identical to the nucleotide sequence of SEQ ID NO: 8661.
See sequence alignment below. NOTE: a nucleic acid sequence that binds to the complement of a template sequence, as recited in claim 17, would be identical to the template sequence, hence the sequence alignment below. Red box = SEQ ID NO:1; Green Box = reference application SEQ ID NO: 8661)
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It would have been prima facie obvious to one of ordinary skill, in the art at the time of the effective filing date, to modify the teachings of disrupting a B2M gene in iPSCs using a gRNA that targets a B2M gene from Izhar and use the gRNA sequence set forth in SEQ ID NO: 8661 from Ando to properly target and edit the B2M gene in iPSCs. One would be motivated to do so to generate cells with edited B2M genes, which is a known technique in the art, and therefore one would have reasonable expectation of success.
Regarding claim 18, the teachings of Izhar and Watanabe render obvious claim 1 and 12.
However, Izhar and Watanabe do not teach wherein the gRNA binds to a complement sequence of any one of SEQ ID NO: 17.
Barghetti teaches a spacer sequence (“The spacer sequence is designed to hybridize with the target nucleotide sequence” (i.e. gRNA) (para 0107)) and “wherein the spacer sequence is capable of hybridizing with the human B2M gene” (para 0111).
More specifically, Barghetti teaches a spacer sequence of SEQ ID NO: 625. When comparing the nucleotide sequence of SEQ ID NO: 625 with the claimed nucleotide sequence of SEQ ID: NO 17 as recited in claim 18, the instant SEQ ID NO: 17 is 100% identical to the nucleotide sequence of SEQ ID NO: 625
See sequence alignment below. NOTE: a nucleic acid sequence that binds to the complement of a template sequence, as recited in claim 18, would be identical to the template sequence, hence the sequence alignment below. Red box = SEQ ID NO:17; Green Box = reference application SEQ ID NO: 625).
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It would have been prima facie obvious to one of ordinary skill, in the art at the time of the effective filing date, to modify the teachings of disrupting a B2M gene in iPSCs using a gRNA that targets a B2M gene from Izhar and use the gRNA (spacer sequence) set forth in SEQ ID NO: 625 from Barghetti to properly target and edit the B2M gene in iPSCs. One would be motivated to do so to generate cells with edited B2M genes, which is a known technique in the art, and therefore one would have reasonable expectation of success.
Regarding claim 19-22, the teachings of Izhar and Watanabe render obvious claim 1 and 12.
However, Izhar and Watanabe do not teach wherein the gRNA comprises or consists of a sequence of SEQ ID NOs: 18.
Donohoue teaches a CRISPR guide RNA that comprises and consists of a sequence of SEQ ID: 416 (para 0149) that targets the B2M gene. When comparing the nucleotide sequence of SEQ ID NO: 416 with the claimed nucleotide of SEQ ID NO: 18 as recited in claim 19-22, the instant SEQ ID NO: 18 is 100% identical to the nucleotide sequence of SEQ ID NO: 416. See sequence alignment below. Red box = SEQ ID NO:18 ; Green Box = reference application SEQ ID NO: 416.)
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It would have been prima facie obvious to one of ordinary skill, in the art at the time of the effective filing date, to modify the teachings of disrupting a B2M gene in iPSCs using a gRNA that targets a B2M gene from Izhar and use CRISPR guide RNA set forth in SEQ ID NO: 416 from Donohoue to properly target and edit the B2M gene in iPSCs. One would be motivated to do so to generate cells with edited B2M genes, which is a known technique in the art, and therefore one would have reasonable expectation of success.
Regarding claim 77, the teachings of Izhar and Watanabe render obvious claim 1.
However, Izhar and Watanabe do not teach wherein the disruption further comprises a knock-in of a polynucleotide encoding a transgene, wherein the polynucleotide is inserted within the B2M gene.
Lee teaches “cells in which the expression of a B2M gene is modulated” and that an exogenous transgene may be integrated into a B2M gene as the modulation (para 0019).
It would have been prima facie obvious to one of ordinary skill, in the art at the time of the effective filing date, to modify the teachings of disrupting a B2M gene in iPSCs using a gRNA that targets a B2M gene from Izhar and Watanabe with the teachings of disrupting the B2M gene by inserting a transgene within the B2M gene from Lee to generate an B2M gene with a transgene insertion within the genome of an iPSC. One would be motivated to do so to disrupt the B2M gene via an insertion that could cause alternative controlling of gene expression, such as inserting an exogenous transgene that is a stop codon, or express a chimeric antigen receptor for cell therapy purposes. As insertion of exogenous transgenes into known gene loci is known in the art, one would have a reasonable expectation of success.
Regarding claim 78, the teachings of Izhar, Watanabe, and Lee render obvious claim 1 and 77. Moreover, Lee teaches that the exogenous transgene encodes an engineered TCR (para 0019), rendering obvious wherein the transgene encodes a chimeric antigen receptor, a TCR, a therapeutic payload or a therapeutic protein.
Regarding claim 79, the teachings of Izhar, Watanabe, and Lee render obvious claim 1 and 77. Moreover, Lee teaches that the exogenous transgene may be integrated into a B2M gene, rendering obvious wherein the polynucleotide is inserted within SEQ ID NO: 1 (i.e. the B2M gene).
Conclusion
Claims 1-13, 16-22, and 77-79 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Juliana Candelaria whose telephone number is (571)272-5488. The examiner can normally be reached Monday - Friday 8am - 5pm.
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/JULIANA IRENE CANDELARIA/ Examiner, Art Unit 1634
/MARIA G LEAVITT/ Supervisory Patent Examiner, Art Unit 1634