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 .
Priority
Acknowledgment is made of applicant’s claim for priority based on a provisional application filed as 62/892,888 on 08/28/2019.
All claims are given the priority date of 08/28/2019.
Application Status
Receipt is acknowledged of amendment, filed 10/07/2025. Claims 1, 15-30 and 32-34 are currently pending.
Election/Restriction
Applicant’s election of Group I, drawn to claims 1 and 15-20 in the reply filed on 10/07/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 21-30 and 32-34 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/07/2025.
Claims 1 and 15-20 are currently under consideration.
Information Disclosure Statement
Receipt of acknowledgment of the information disclosure statements filed on 10/06/2022 and 10/07/2025 have been received and all references have been considered.
Claim Objections
Claim 1 is objected to because of the following informalities:
Claim 1 recites the abbreviation of “gRNA”. The first instance of the term must be spelled out and the abbreviation placed in parenthesis next to it such as, “guide RNA (gRNA)”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claims 15 and 16 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 15 and 16 is indefinite for being incomplete in themselves. It is noted that “Table 1, 2, 6 or 8” is recited in claims 15 and 16 are merely populated exclusively by sequences, and there is no reason, other than inconvenience, that the sequences cannot be recited in the claims. See MPEP 2173.05(s): “Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience”. It is also important to note that the claim recites “a targeting domain which binds a target domain of Table 1, 2, 6, or 8” wherein the phrase “a targeting domain” is interpreted to mean two or more consecutive nucleotides of the sequences listed in Tables 1, 2, 6 or 8. It is unclear whether the entire sequence would be required for the successful targeting of the targeting domain.
Appropriate correction is required.
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 and 15-18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Qin et al (Molecular Therapy, Vol. 27 No. 7, Pgs. 1262-1274; July 2019) as evidenced by Sanjana et al (Nat Methods 11, 783–784; 2014) and Jinek et al (Science337,816-821; 2012).
Regarding claim 1, the claim recites “a sequence of any one of SEQ ID NOs: 21-30 or 48-51” wherein the phrase “a sequence” is interpreted to mean two or more consecutive nucleotides of the elected SEQ ID NO: 50.
Qin teaches expressed on the surface of a variety of hematologic neoplasms, the interleukin-3 (IL-3) receptor alpha subunit (IL3Ra), also known as CD123, has been under investigation as a therapeutic target for hairy cell leukemia, acute myelogenous leukemia (AML), and acute lymphoblastic leukemia (ALL) (Page 1263, Column 1). Qin teaches targeting CD123 via CRISPR by transducing the cells with LentiCRISPRv2 transfer vector containing the guide RNA for targeting CD123 where the guide RNA is 5’-AGTTCCCACATCCTGGTGCG-3’ (Page 1270, Column 2) (See Appendix I).
Regarding Claims 15 and 16, the claim recites “a targeting domain which binds a target domain of Table 1, 2, 6, or 8” wherein the phrase “a targeting domain” is interpreted to mean two or more consecutive nucleotides of the sequences listed in Tables 1, 2, 6 or 8.
Qin teaches the targeting CD123 via CRISPR by transducing the cells with LentiCRISPRv2 transfer vector containing the guide RNA for targeting CD123 where the guide RNA is 5’-AGTTCCCACATCCTGGTGCG-3’ (Page 1270, Column 2) (See Appendix I) where the guide RNA is capable of targeting the target domain listed in instant Table 1 such as instant SEQ ID NO: 9 (See Appendix II).
Regarding claims 17 and 18, Qin teaches the gRNA sequence as 5’-AGTTCCCACATCCTGGTGCG-3’ (Page 1270, Column 2). Sanjana is only cited to provide that the guide RNA of lenticrisperv2 is a single guide RNA (sgRNA) (i.e., it is one piece and not a separate crRNA and tracrRNA) (Page 783, Table 1). Because Qin teaches that the guide RNA is a single guide RNA, it would also teach the limitations of claim 17 as evidenced by Jinek which teaches the known structure of Cas9 sgRNA comprising a first complementarity domain, a linking domain and a second complementarity domain complementary to the first complementarity domain, and a proximal region wherein the first and second domains hybridize to form a stem-loop structure with GAAA as the loop or linking domain of the claim and the sequence that hybridizes to the target is the proximal region of the claim (Page 820, Figure 5).
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.
Claims 1 and 15-20 are rejected under 35 U.S.C. 103 as being unpatentable over Qin et al (Molecular Therapy, Vol. 27 No. 7, Pgs. 1262-1274; July 2019) in view of Glucksmann et al (WO 2015/048577 A2) and as evidenced by Sanjana et al (Nat Methods 11, 783–784; 2014) and Jinek et al (Science337,816-821; 2012).
Qin teaches expressed on the surface of a variety of hematologic neoplasms, the interleukin-3 (IL-3) receptor alpha subunit (IL3Ra), also known as CD123, has been under investigation as a therapeutic target for hairy cell leukemia, acute myelogenous leukemia (AML), and acute lymphoblastic leukemia (ALL) (Page 1263, Column 1). Qin teaches the targeting CD123 via CRISPR by transducing the cells with LentiCRISPRv2 transfer vector containing the guide RNA for targeting CD123 where the guide RNA is 5’-AGTTCCCACATCCTGGTGCG-3’ (Page 1270, Column 2) (See Appendix I) where the guide RNA is capable of targeting the target domain listed in instant Table 1 such as instant SEQ ID NO: 9 (See Appendix II). Qin teaches the gRNA sequence as 5’-AGTTCCCACATCCTGGTGCG-3’ (Page 1270, Column 2). Sanjana is only cited to provide that the guide RNA of lenticrisperv2 is a single guide RNA (sgRNA) (i.e., it is one piece and not a separate crRNA and tracrRNA) (Page 783, Table 1). Because Qin teaches that the guide RNA is a single guide RNA, it would also teach the limitations of claim 17 as evidenced by Jinek which teaches the known structure of Cas9 sgRNA comprising a first complementarity domain, a linking domain and a second complementarity domain complementary to the first complementarity domain, and a proximal region wherein the first and second domains hybridize to form a stem-loop structure with GAAA as the loop or linking domain of the claim and the sequence that hybridizes to the target is the proximal region of the claim (Page 820, Figure 5).
Qin does not teach the specific gRNA sequence of SEQ ID NO: 50.
Glucksmann teaches optimization of guide RNA by analyzing specific parts of the genome that would increase the efficiency of genome editing wherein cleavage efficiency at each off-target sequences can be predicted and guide RNAs with increased off-targeting effects can be avoided [0456]. Glucksmann teaches the guide RNA is preceding an NGG PAM within the genome [0456]. Glucksmann teaches the gRNA is 20 nucleotides in length [0604]. Glucksmann teaches the target position may comprise one or more nucleotides that are altered, e.g., corrected, by a template nucleic acid and the target position is within a target sequence (e.g., the sequence to which the gRNA binds) [0573].
The gRNA provided by the instant application is shown within the human genome of the X chromosome at positions 1352337 to 1352356 (See alignment below; See Appendix III).
PNG
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43
687
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Greyscale
Wherein position 1 corresponds to position 1352301 within the genome, the underlined portion is the gRNA as claimed in the instant application and directly following is the required PAM sequence of CGG (highlighted for clarity) for the construction of the guide RNA to the target gene with increased specificity.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the guide RNA of Qin by utilizing the computational gRNA selection process to select gRNAs that would provide increased efficiency of on-target events as well as reduced interactions with off-target events as taught by Glucksmann, wherein the relevant artisan would have determined, with a reasonable expectation of success through routine screening/optimization assays, the guide RNA sequence of instant SEQ ID NO: 50 in view Qin’s teachings that include the targeting of CD123 using a gRNA CRISPR cas system and Glucksmann’s teaching of the gRNA design methods that are known in the art.
One of ordinary skill in the art would have been motivated to do so to increase the efficiency of the guide RNA used for targeting CD123, also referred to as IL3RA, by targeting the specific sequence of instant SEQ ID NO: 50 because guide RNA for targeting CD123 as well as guide RNA design methods and techniques are known in the art as evidenced by Qin and Glucksmann.
One of ordinary skill in the art would have been further motivated to incorporate the basic design rules of guide RNAs, including a single gRNA comprising a first complementarity domain, a linking domain, a second complementarity domain which is complementary to the first complementarity domain, and a proximal domain, wherein the guide RNA is a single guide RNA (sgRNA) and comprises one or more 2'O-methyl nucleotide and one or more phosphorothioate or thioPACE linkages, as taught by Glucksmann in paragraphs [0188, 0362, 0915 and 0946] in order to target the CD123 gene, also known as IL3RA, for gene manipulation. Regarding claims 15-20, although Qin teaches expressed on the surface of a variety of hematologic neoplasms, the interleukin-3 (IL-3) receptor alpha subunit (IL3Ra), also known as CD123, has been under investigation as a therapeutic target for hairy cell leukemia, acute myelogenous leukemia (AML), and acute lymphoblastic leukemia (ALL) (Page 1263, Column 1) as well as targeting CD123 via CRISPR by transducing the cells with LentiCRISPRv2 transfer vector containing the guide RNA (Page 1270, Column 2), Qin does not teach the specific gRNA sequence of instant SEQ ID NO: 50. Glucksmann futher teaches the guide RNA as unimolecular such as having a single RNA molecule [0188]. Glucksmann teaches IL3RA as a target gene that the gRNA can be used to target for gene manipulation ([0846] and Table IX, Page 445). Glucksmann teaches a gRNA that has the following structure: 5' [targeting domain]- [first complementarity domain]- [linking domain]- [second complementarity domain]- [proximal domain]- [tail domain]-3' [0362]. Glucksmann teaches the guide RNA as a modified guide such as all, or substantially all, of the phosphate groups of a unimolecular or modular gRNA molecule are replaced with phosphorothioate groups [0915]. Glucksmann teaches the guide RNA are 2'-sugar modified, such as, 2-F 2'-0-methyl [0946].
In view of the foregoing, claims 1 and 15-20 taken as a whole would have been prima facie obvious at the time the invention was made.
Conclusion
No claims are allowed.
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/ALEXANDRA ROSE LIPPOLIS/Examiner, Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637