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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 05/18/2026 has been entered.
This action is in response to the amendment filed 05/18/2026, in which claims 1 were amended and claims 3, 16, 19, 21, 22, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62 and 121 were previously presented. Claims 1, 3, 16, 19, 21, 22, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62 and 121 are currently pending. Claims 26, 28, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60 and 62 were previously withdrawn due to a restriction requirement made in the Office Action mailed on 09/09/2025.
Therefore, claims 1, 3, 16, 19, 21, 22, 30 and 121 are currently under examination.
Applicant’s arguments have been thoroughly reviewed, but are not persuasive for the
reasons that follow. Any rejection and objections not reiterated in this action have been
withdrawn.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.
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 1, 3, 16, 19, 21, 22, 30 and 121 are rejected under 35 U.S.C. 102(a)(l)/(a)(2) as being anticipated by Welstead et al (WO 2017/152015 Al) as evidenced by Ungerer et al (Sci Rep 6, 39681, pgs. 1-9;2016). This rejection was made in the Office action mailed 09/09/2025 and has been rewritten to address the amendment to the claims in the reply filed 12/08/2025.
Regarding claims 1 and 30, Welstead teaches an isolated or nonnaturally occurring gRNA molecule, comprising a targeting domain which is complementary with a target domain from one T-cell expressed gene selected from the group consisting of FAS, BID, CTLA4, PDCDl, CBLB, PTPN6, B2M, TRAC and TRBC Gene (Page 8, Lines 17-21).Welstead teaches a T cell target position can be targeted (e.g. altered) by gene editing, e.g., using CRISPR-Cpfl mediated methods to target (e.g. alter) in one or more T cell expressed genes, e.g., B2M (Page 27, Lines 1-4). Welstead teaches when the T cell target knockout position is the B2M coding region, e.g., an early coding region, and more than one gRNA is used to position breaks, e.g., two double stranded breaks, e.g., to create one or more indels, in the target nucleic acid sequence, each guide RNA is independently selected from SEQ ID NOS: 3095-3283 (Page 11, Lines 28-32). Welstead teaches SEQ ID NO: 3119 is 100% identical to instant SEQ ID NO: 625 (See Appendix I). Welstead teaches gRNA where the 5' end is the direct repeat domain with a stem and loop hairpin structure (comprising the modulator nucleic acid of the claim) and the 3' end is a targeting domain (Page 103, Figure 1). Welstead teaches the gRNA comprises two nucleic acids are separate with one nucleic acid comprising the targeter nucleic acid sequence (referred to as the targeting domain) and the other nucleic acid comprising the modular nucleic acid sequence (Page 32, Lines 10-16 and Page 84, Line 31 bridging Page 85, Line 2). Ungerer is only cited to show that the Cpfl is a type V-A nuclease of the class II family of CRISPR systems (Page 1, Paragraph 3).
Regarding claim 3, Welstead teaches an isolated or non-naturally occurring gRNA
molecule, comprising a targeting domain (spacer sequence of the claim) which is complementary
with a target domain from one T-cell expressed gene selected from the group consisting of FAS,
BID, CTI.A4, PDCDl, CBLB, PTPN6, B2M, TRAC and TRBC Gene (Page 8, Lines 17-21).
Welstead teaches gRNA where the 5' end is the direct repeat domain with a stem and loop
hairpin structure (comprising the targeter stem sequence of the claim) and the 3' end is a
targeting domain (spacer sequence of the claim) (Page 103, Figure 1).
Regarding claims 16 and 19, Welstead teaches the guide RNA is chemically modified
with 2'-O-methoxyethyl (Page 82, Lines 20-30).
Regarding claim 21, Welstead teaches the use of the Cpfl molecule in conjunction with the gRNA for nuclease acitivity (Page 58, Lines 14-16). Ungerer is only cited to show that the Cpfl is a type V-A nuclease of the class II family of CRISPR systems (Page 1, Paragraph 3).
Regarding claim 22, Welstead teaches the Cpfl molecule and gRNA form a Ribonucleoprotein (RNP) complex (Page 71, Lines 12-13).
Regarding claim 121, Welstead teaches an isolated or nonnaturally occurring gRNA molecule, comprising a targeting domain which is complementary with a target domain from one T-cell expressed gene selected from the group consisting of FAS, BID, CTLA4, PDCDl, CBLB, PTPN6, B2M, TRAC and TRBC Gene (Page 8, Lines 17-21).Welstead teaches a T cell target position can be targeted (e.g. altered) by gene editing, e.g., using CRISPR-Cpfl mediated methods to target (e.g. alter) in one or more T cell expressed genes, e.g., B2M (Page 27, Lines 1-4). Welstead teaches when the T cell target knockout position is the B2M coding region, e.g., an early coding region, and more than one gRNA is used to position breaks, e.g., two double stranded breaks, e.g., to create one or more indels, in the target nucleic acid sequence, each guide RNA is independently selected from SEQ ID NOS: 3095-3283 (Page 11, Lines 28-32). Welstead teaches SEQ ID NO: 3119 is 100% identical to instant SEQ ID NO: 625 (See Appendix I).
Response to Arguments - Claim Rejections - 35 USC § 102
The rejection of claims 1, 3, 5, 6, 16, 19-22, 24, 25 and 30 under 35 U.S.C. 103 as being anticipated by Welstead et al (WO 2017/152015 Al) as evidenced by Ungerer et al (Sci Rep 6, 39681, pgs. 1-9;2016) has been maintained in view of Applicant' s amendment to the claims.
Applicant’s arguments have been fully considered and have not been found persuasive. Applicant argues Welstead fails to teach a combination of a targeter nucleic acid and a modulator nucleic acid which, when combined, are capable of activating a type V-A Cas nuclease as claimed. Applicant continues that Welstead merely discloses single guide nucleic acids and that this is in line with naturally occurring Type V-A CRISPR-Cas systems which lack a tracrRNA and rely on a single crRNA to guide the CRISPR-Cas complex to the target DNA. Applicant argues that the same applies to the remaining dependent claims.
These arguments are not found to be persuasive because Welstead teaches the gRNA comprises two nucleic acids are separate with one nucleic acid comprising the targeter nucleic acid sequence (referred to as the targeting domain) and the other nucleic acid comprising the modular nucleic acid sequence (Page 32, Lines 10-16 and Page 84, Line 31 bridging Page 85, Line 2).
Therefore, all of the limitations of claim 1 are anticipated by Welstead as evidenced by Ungerer and the rejection is proper.
Conclusion
No claims are allowed.
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/ALEXANDRA ROSE LIPPOLIS/Examiner, Art Unit 1637
/CELINE X QIAN/Primary Examiner, Art Unit 1637
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