DETAILED ACTION
Claims 1, 2, 6, 8, 9, 11, 13, 14, 18, 20, 23, 25, 29-31, 33, 35-38, 46, 48, 52, 53, 56, 59, 61, 63-66, 69, 72, and 73 from the claim set filed July 1, 2026 are pending. Claims 3-5, 7, 10, 12, 15-17, 19, 21, 22, 24, 26-28, 32, 34, 39-45, 47, 49-51, 54, 55, 57, 58, 60, 62, 67, 68, 70, and 71 are cancelled. Claims 1, 2, 6, 8, 9, 11, 13, 14, 18, 20, 23, 25, 29-31, 33, 36, 46, 48, 52, 56, 61, 63-66, 69, 72, and 73 are withdrawn. Claims 35, 37, 38, 53, and 59 are being examined on the merits herein.
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
Applicant’s election without traverse of Group III, claims 35, 37, 38, 53, 59, and 61, drawn to a method of making an engineered cell, and further, Applicants election without traverse of 2 species of CIITA guide RNA SEQ ID NOs, i.e., SEQ ID NOS: 27 and 32, in the reply filed July 1, 2026 is acknowledged.
Examiner inadvertently included claim 61 in Group III, drawn to a method of making an engineered cell. However, as noted in the restriction filed April 1, 2026, claim 61 solely makes up Group V, drawn to an engineered cell. As such, claim 61 is withdrawn, as being drawn to a non-elected invention, i.e., Group V.
Thus, claims 1, 2, 6, 8, 9, 11, 13, 14, 18, 20, 23, 25, 29-31, 33, 36, 46, 48, 52, 56, 61, 63-66, 69, 72, and 73 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 35, 37, 38, 53, and 59 will be examined on the merits herein.
Priority
A claim for benefit of a prior-filed application under 35 U.S.C. 119(a)-(f) or under 35
U.S.C. 120, 121, 365(a)-(c), 386 (a) or 386(c) has been made. The effective filing date of the
present application is December 23, 2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 7/1/2026, 12/11/2025, and 11/13/2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
Examiner notes the lengthy specification (333 pages) has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware of in the specification.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/patents-application- process/filing-online/legal-framework-efs-web), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification (Tables 2 and 3) are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Tables 2 and 3 contain sequences not identified with a sequence identifier (i.e., exemplary guide RNA full sequences must be identified in each row with the specific SEQ ID NO (Table 2) and i.e., exemplary full sequences must be identified in each row with the specific SEQ ID NO (Table 3)). As an example, as currently written, Table 2 notes for the full column of exemplary guide RNA full sequences that said column comprises SEQ ID NOs: 218-334.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—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 or joint inventor of carrying out the invention.
Claim 35, 37, 38, and 53 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
From M.P.E.P 2163, the analysis of whether the specification complies with the written description requirement calls for the examiner to compare the scope of the claims with the scope of the description to determine whether applicant has demonstrated possession of the claimed invention from the standpoint of one of skill in the art at the time the application was filed. For inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession.
For claims drawn to a genus, possession may be shown (for example) through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. A “representative number of species” means that the species which are adequately described are representative of the entire genus, and is an inverse function of the skill and knowledge in the art. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly. If a representative number of adequately described species are not disclosed for a genus, the claim to that genus must be rejected as lacking adequate written description under 35 U.S.C. 112, paragraph 1.
Claim 35 recites the subject matter necessitating the instant rejection and is drawn to:
“A method of making an engineered cell, which has reduced or eliminated surface expression of MHC class II protein relative to an unmodified cell, comprising contacting a cell with a composition comprising:
(a) a CIITA guide RNA comprising
a guide sequence selected from SEQ ID NOs 27 and 32;
at least 17, 18, 19, or 20 contiguous nucleotides of a sequence selected from SEQ ID NOs: 27 and 32;
a guide sequence at least 95%, 90% or 85% identical to a sequence selected from SEQ ID NOs: 27 and 32;
or
As noted supra, Applicant elected SEQ ID NOs: 27 and 32 as the species of CIITA guide RNA, thus, for purposes of examination, points iv – vii have been struck through as not reading on the elected species.
Claim 35 recites a structure, i.e., SEQ ID NOs: 27 and 32. Claim 35 also requires a function, i.e., reducing or eliminating surface expression of MHC class II protein via contacting a cell with the claimed guide RNAs. Thus, said guide RNAs must be capable of binding to the target sequence.
While it may be granted that the structure of SEQ ID NOs: 27 and 32 are capable of providing for the function of binding to the target sequences, there is insufficient description of a representative sample of structures that are as little as a 2mer (i.e., point (i) a guide sequence selected from SEQ ID NOs 27 and 32) or comprise as little as 17, 18, or 19 contiguous nucleotides of said gRNAS (i.e., point (ii) at least 17, 18, 19, or 20 contiguous nucleotides of a sequence selected from SEQ ID NOs: 27 and 32), or comprise as little as 85-95% identity to said gRNAs (i.e., point (iii) a guide sequence at least 95%, 90% or 85% identical to a sequence selected from SEQ ID NOs: 27 and 32) that are capable of providing for said function as claimed.
In assessing support for the instant invention, the application may draw from both the prior art as well as the instant specification in order to comply with the written description requirement. With regard to the specification, it is noted that only SEQ ID NOs: 27 and 32 per se have been shown capable of providing for the claimed function. Applicant has not demonstrated any variant capable of the claimed function. Accordingly, the instant specification alone does not provide sufficient representative sampling of structures that are as little as a 2mer, as little as 17 contiguous nucleotides, or as little as 85% identical, etc. that are capable of providing for said function as claimed. Examiner notes the extensive number of sequences encompassed within the instant application and welcomes Applicant to point Examiner to the specific variant sequences encompassed by the application that are capable of the claimed function.
In turning to the prior art, it is noted that the prior art teaches sequences with 100% identity to SEQ ID NOs; 27 and 32. However, the prior art does not teach structures that are as little as a 2mer, as little as 17 contiguous nucleotides, or as little as 85% identical, etc. that are capable of providing for said function as claimed.
Finally, it is considered well accepted that extrapolation from the primary sequence structures of nucleotides and/or polypeptide sequences to predict function in a physiological setting is highly unpredictable. It is considered scientific consensus that changing out amino acids and/or nucleotides within a sequence is capable of altering or even eliminating function. Accordingly, the combination of a lack of representative sampling of structures that reside within the genus of structures that are as little as a 2mer (i.e., point (i) a guide sequence selected from SEQ ID NOs 27 and 32) or comprise as little as 17, 18, or 19 contiguous nucleotides of said gRNAS (i.e., point (ii) at least 17, 18, 19, or 20 contiguous nucleotides of a sequence selected from SEQ ID NOs: 27 and 32), or comprise as little as 85-95% identity to said gRNAs (i.e., point (iii) a guide sequence at least 95%, 90% or 85% identical to a sequence selected from SEQ ID NOs: 27 and 32) that are capable of providing for said function as claimed combined with the high unpredictability of using sequences to understand physiological function is sufficient to consider the breadth of claim 35 and those dependent thereon as lacking sufficient written support over the scope claimed.
Thus, claims 35, 37, 38, and 53 are properly rejected.
Claims 35, 37, 38, and 53 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claim 35 recites the subject matter necessitating the instant rejection and is drawn to:
“A method of making an engineered cell, which has reduced or eliminated surface expression of MHC class II protein relative to an unmodified cell, comprising contacting a cell with a composition comprising:
(a) a CIITA guide RNA comprising
a guide sequence selected from SEQ ID NOs 27 and 32;
at least 17, 18, 19, or 20 contiguous nucleotides of a sequence selected from SEQ ID NOs: 27 and 32;
a guide sequence at least 95%, 90% or 85% identical to a sequence selected from SEQ ID NOs: 27 and 32;
or
As noted supra, Applicant elected SEQ ID NOs: 27 and 32 as the species of CIITA guide RNA, thus, for purposes of examination, points iv – vii have been struck through as not reading on the elected species.
The specification, while being enabling for the single species of a guide RNA consisting of SEQ ID NOs: 27 and 32 (i.e., 100% identity), does not reasonably provide enablement for the genus of gRNA that are as little as a 2mer (i.e., point (i) a guide sequence selected from SEQ ID NOs 27 and 32) or comprise as little as 17, 18, or 19 contiguous nucleotides of said gRNAS (i.e., point (ii) at least 17, 18, 19, or 20 contiguous nucleotides of a sequence selected from SEQ ID NOs: 27 and 32), or comprise as little as 85-95% identity to said gRNAs (i.e., point (iii) a guide sequence at least 95%, 90% or 85% identical to a sequence selected from SEQ ID NOs: 27 and 32) that are capable of providing for the claimed function of target sequence binding in order to make an engineered cell, as claimed in claim 35. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with this claim. Dependent claims 37, 38, and 53 either depend directly from claim 35 or incorporate the method of claim 35.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.” See MPEP § 2164. These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill:
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples;
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Breadth of the claims:
With respect to the breadth of the claims, the claims as currently drafted encompass the genus of SEQ ID Nos: 27 and 32 gRNAs that are as little as a 2mer (i.e., point (i) a guide sequence selected from SEQ ID NOs 27 and 32) or comprise as little as 17, 18, or 19 contiguous nucleotides of said gRNAS (i.e., point (ii) at least 17, 18, 19, or 20 contiguous nucleotides of a sequence selected from SEQ ID NOs: 27 and 32), or comprise as little as 85-95% identity to said gRNAs (i.e., point (iii) a guide sequence at least 95%, 90% or 85% identical to a sequence selected from SEQ ID NOs: 27 and 32). Consequently, the breadth of the claims is expansive.
Nature of the invention:
The invention is in the field of gene editing.
The state of the prior art and predictability in the art:
With respect to the state of the prior art, and predictability of the art, at the time of filing the instant invention, gRNAs with 100% sequence identity to SEQ ID NOs: 27 and 32 were known. Please see the 102 rejections below.
However, as evidenced by Saeed (Saeed, et al., Biotechnology Journal (2026) 21: e70255; PTO 892), CRISPR-based genome and transcriptome editing technologies have emerged as powerful tools for therapeutic, agricultural, and industrial applications. However, their broader clinical and translational use remains limited by variable guide RNA (gRNA) or single-guide RNA (sgRNA) efficiency and unintended off-target activity, which may lead to genotoxic effects and major safety concerns (Abstract). Saeed evidences off-target risk can vary, and on-target efficiency can vary among sgRNAs targeting different loci; the results of editing have been shown to depend on the composition of the guide sequences, the locus context, and cell status. Both systematic sgRNA engineering, with large empirical studies to derive optimized design rules, and predictive performance (at least within cell types and across experimental settings and CRISPR modalities) have proven challenging (p2, 1st column, 2nd paragraph). Further, Saeed evidences these scientific constraints are also accompanied by ethical and safety issues, which increase as CRISPR systems approach actual use (p2, 1st column, 3rd paragraph).
Consequently, there is reason to conclude that there would be a high degree of unpredictability in SEQ ID Nos: 27 and 32 gRNAs that are as little as a 2mer (i.e., point (i) a guide sequence selected from SEQ ID NOs 27 and 32) or comprise as little as 17, 18, or 19 contiguous nucleotides of said gRNAS (i.e., point (ii) at least 17, 18, 19, or 20 contiguous nucleotides of a sequence selected from SEQ ID NOs: 27 and 32), or comprise as little as 85-95% identity to said gRNAs (i.e., point (iii) a guide sequence at least 95%, 90% or 85% identical to a sequence selected from SEQ ID NOs: 27 and 32) that are capable of accurately binding to the target sequences.
Guidance of the Specification/Working Examples:
Applicants have not provided working examples encompassing the genus of gRNAs discussed above. Applicants have provided a working example for the species of gRNAs having 100% identity to SEQ ID NOs: 27 and 32. The absence of working examples directed to the genus of gRNAs claimed, necessitates further experimentation. Therefore, the specification does not provide sufficient guidance on how to make and use the claimed genus of gRNAs.
The Quantitation of Experimentation Required:
Undue experimentation would be required to practice the invention as claimed due to the amount of experimentation necessary because of the expansive breadth of the claims, the state of the prior art and its lack of predictability, and the lack of guidance in the form of working examples in the specification.
MPEP §2164.01(a), provides that “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1157, 1562; 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
After applying the Wands factors and analysis to claims 35, 37, 38, and 53, in view of the Applicant’s entire disclosure, it is concluded that the practice of the invention as claimed in said claims, would not be enabled by the written disclosure. Therefore, claims 35, 37, 38, and 53 are rejected under 35 U.S.C. §112(a) for failing to disclose sufficient information to enable a person of skill in the art to make the invention commensurate in scope with the claims.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 35, 37, 38, 53, and 59 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Harvard (US Patent No. 10,968,426, published April 6, 2021 (EFD of WO 2016/183041 A2, published November 17, 2016); PTO 892).
For ease of sequence alignment and access to sequences, Examiner used US Patent No. 10,968,426. Examiner verified said sequences are encompassed within WO 2016/183041 A2.
In regards to claims 35, 37, and 59, and as noted supra, Applicant elected CIITA guide RNA SEQ ID NOs: 27 and 32 as the species of sequence gRNA to be searched.
Thus, claim 35 now reads: “A method of making an engineered cell, which has reduced or eliminated surface expression of MHC class II protein relative to an unmodified cell, comprising contacting a cell with a composition comprising:
(a) a CIITA guide RNA comprising
a guide sequence selected from SEQ ID NOs 27 and 32;
at least 17, 18, 19, or 20 contiguous nucleotides of a sequence selected from SEQ ID NOs: 27 and 32;
a guide sequence at least 95%, 90% or 85% identical to a sequence selected from SEQ ID NOs: 27 and 32;
or
Claim 37 now reads: The method of claim 35, wherein the CIITA guide RNA comprises
(i) a guide sequence selected from SEQ ID NOs: 27 and 32;
(ii) at least 17, 18, 19, or 20 contiguous nucleotides of a sequence selected from SEQ ID NOs: 27 and 32;
(iii) a guide sequence at least 95%, 90%, or 85% identical to a sequence selected from SEQ ID NOs: 27 and 32.
Claim 59 now reads: The method of claim 35, wherein
(i)
(ii) the CIITA guide RNA comprises any one of sequences SEQ ID NOs: 27 and 32; or
(iii)
Thus, claim 59 requires the CIITA guide RNA to have 100% identity to SEQ ID NO: 27 or 32.
Harvard teaches the use of genome editing tools such as a TALEN and/or CRISPR in human pluripotent stem cells to reduce expression or knock out the highly polymorphic classical MHCII genes (Column 1, lines 53-57). Harvard teaches such reduced expression or knock out of the MHCII genes is accomplished via directly and/or indirectly targeting CIIA genes (Column 1, lines 57-62). Harvard teaches of human stem cells that do not express CIITA (Column 2, lines 55-60). Harvard teaches of hypoimmunogenic (i.e., less likely to trigger an immune response) stem cells comprising a modified genome comprising a genomic modification in which the CIITA gene has been edited to delete a first contiguous stretch of genomic DNA, thereby reducing or eliminating CIITA surface expression and/or activity in the cell (i.e., as compared to an unmodified cell), wherein the first contiguous stretch of genomic DNA has been deleted by contacting the cell with a Cas protein or a nucleic acid encoding a Cas protein and a first pair of ribonucleic acids (i.e., a CIITA gRNA sequence) having sequences selected from the group consisting of SEQ ID NOs: 5184-36352 (i.e., of which SEQ ID NO: 12,131 is encompassed) (Column 5, lines 62-67 – Column 6, lines 1-13). As is shown below in the sequence alignment of SEQ ID NO: 32 (i.e., Qy) of the instant application to SEQ ID NO: 12,131 (i.e., Db) of Harvard, said sequences have 100% identity.
Qy = SEQ ID NO: 32 of the instant application, Db = SEQ ID NO: 12,131 of Harvard
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96
290
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Greyscale
Thus, Harvard teaches of a method of making an engineered cell, which has reduced or eliminated surface expression of MHC class II protein relative to an unmodified cell, comprising contacting a cell with a composition comprising a CIITA guide RNA with 100% identity to SEQ ID NO: 32. Thus, Harvard anticipates claims 35, 37, and 59.
Further, Examiner notes SEQ ID NO: 15,034 of Harvard has 100% identity to SEQ ID NO: 27 of the instant application. As noted supra, Harvard teaches of hypoimmunogenic stem cells comprising a modified genome comprising a genomic modification in which the CIITA gene has been edited to delete a first contiguous stretch of genomic DNA, thereby reducing or eliminating CIITA surface expression and/or activity in the cell (i.e., as compared to an unmodified cell), wherein the first contiguous stretch of genomic DNA has been deleted by contacting the cell with a Cas protein or a nucleic acid encoding a Cas protein and a first pair of ribonucleic acids (i.e., a CIITA gRNA sequence) having sequences selected from the group consisting of SEQ ID NOs: 5184-36352 (i.e., of which SEQ ID NO: 15,034 is encompassed) (Column 5, lines 62-67 – Column 6, lines 1-13).
Qy = SEQ ID NO: 27 of the instant application, Db = SEQ ID NO: 15, 034 of Harvard
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131
541
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Greyscale
Thus, Harvard teaches of a method of making an engineered cell, which has reduced or eliminated surface expression of MHC class II protein relative to an unmodified cell, comprising contacting a cell with a composition comprising a CIITA guide RNA with 100% identity to SEQ ID NO: 27.
Thus, Harvard anticipates claims 35, 37, and 59.
In regards to claim 38, Harvard teaches the method of claim 35. Further, Harvard teaches of reducing or knocking out expression of MHC class I genes (HLA-A, HLA-B and HLA-C) (Column I, lines 55-57). Additionally, Harvard teaches of human stem cells that do not express B2M (i.e., a B2M-/- knockout mutant stem cell) and further teaches of human stem cells that do not express one or more of HLA-A, HLA-B and HLA-C (Column 2, lines 55-65). As a POSITA will appreciate, knocking out B2M and HLA-A reads on reducing or eliminating surface expression of B2M and HLA-A proteins in the cell relative to an unmodified cell.
Thus, Harvard anticipates claim 38.
In regards to claim 53, Harvard teaches the method of claim 35. Further, Harvard teaches wherein the CIITA guide RNA is provided to the cell in a vector. Harvard teaches a lentiviral vector “which acts to bring in the guide” (Fig 16D). Additionally, Harvard teaches nucleic acids encoding Cas protein and nucleic acids encoding the at least one to two ribonucleic acids (i.e., gRNA) are introduced into a cell via viral transduction (i.e., lentiviral transduction) (Column 23, lines 25-30).
Thus, Harvard anticipates claim 53.
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHERINE R SMALL whose telephone number is (703)756-4783. The examiner can normally be reached Monday - Friday 8:30am-4pm.
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/KATHERINE R SMALL/Examiner, Art Unit 1633
/EVELYN Y PYLA/Primary Examiner, Art Unit 1633
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