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
Applicant’s claim to priority from International Application No. PCT/US22/18829 filed 03/04/2022 and from US Provisional Application No. 63/156,443 filed 03/04/2021 is hereby acknowledged.
Election/Restrictions
Applicant's election with traverse of Invention Group I (Claims 1-12) and Species A(a (An RNA spacer having 90% identity to SEQ ID NO: 122), B (SEQ ID NO: 122, with gRNA of SEQ ID NO: 30), C (1 (U6 promoter)) and D( AAV9) in the reply filed on 06/08/2026 is acknowledged. The traversal is on the ground(s) that the reference Ruan (Ruan, X. et al. WO 2016/186772 A2, published Nov. 24, 2016; cited on IDS filed 11/27/2023) does not break unity based on sequence homology of 92.2% to 98.8% compared to SEQ ID Nos: 1,2 and 3 of instant Application. This is not found persuasive because Applicant’s arguments are based on amendments of claims to cite SEQ ID Nos: 93-184 and remove SEQ ID NOs: 1, 2 and 3 filed on 06/08/2026, while the restriction requirement was based on claims as filed with preliminary amendments filed on 04/15/2024.
The requirement is still deemed proper and is therefore made FINAL.
Claims 13-18 and 27-31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 06/08/2026.
Application Status
This Application is a National Entry phase Application under 35 U.S.C. § 371 of the International Application No. PCT/US22/18829 filed 03/04/2022.
This Office Action is in response to Applicant’s amendments and arguments filed on 06/08/2026. Amendments to claims filed on 06/08/2026 are hereby acknowledged.
Claims 1, 12, and 18 are currently amended. Claims 19-26 and 32 are cancelled.
Claims 13-18 and 27-31 are withdrawn from consideration. Therefore, claims 1-18 and 27-31 are pending, but only claims 1-12 are under consideration in this Office Action.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 11/27/2023 and 01/02/2026 are hereby acknowledged. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
However, 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, or cited on a submitted IDS, they have not been considered.
Drawings
The Drawing sheets filed 08/28/2023 are hereby acknowledged and are acceptable.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see [0069]). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The use of the terms “In-Fusion” ([00134]-[00135]), “rAPid DNA Dephos & Ligation” ([00134]-[00135]), “Lipofectamine” ([00139], [00141]), “Hyclone” ([00139]), “PromoCell” ([00139], [00149], [00158]), “EnGen” ([00141]), “DNeasy” ([00141]), “ChemiDoc” ([00141]), “Triton X-100”, “ProLong” ([00143]), “Alexa Fluor 568”, “Alexa Fluor 488” ([00143], [00145]), “TRIzol”, “RevertAid ([00149], [00158]), which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore, the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
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 1-11 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by Hsu (Hsu, P.D. et al. US 2019/0048337 A1, published February 14, 2019).
Regarding claim 1, It recites “A nucleic acid comprising:
a nucleotide sequence encoding an RNA spacer sequence comprising at least 90% identity to the sequence set forth in any one of SEQ ID Nos: 93-184;
a nucleotide sequence encoding
the RNA spacer sequence set forth in any one of SEQ ID Nos: 93-184;”
and it also recites:
“(c ) a nucleotide sequence comprising an RNA spacer sequence comprising at least 90% identity to the sequence set forth in any one of SEQ ID Nos: 93-184” and in (d), it recites “ a nucleotide sequence comprising (i) the RNA spacer sequence set forth in any one of SEQ ID Nos: 93-184”.
A search for the sequence SEQ ID NO: 99 (Qy = Query) of instant Application, leads to the following results (Db = Database):
RESULT 1
US-15-732-190-132602
Sequence 132602, US/15732190
Publication No. US20190048337A1
GENERAL INFORMATION
APPLICANT: EDITAS MEDICINE
APPLICANT: HSU, Patrick David
APPLICANT: MAEDER, Morgan Lee
APPLICANT: ODONNELL, Penrose
APPLICANT: TYCKO, Joshua C.
APPLICANT: HUSTON, Nicholas C.
TITLE OF INVENTION: CRISPR/CAS-RELATED METHODS AND COMPOSITIONS FOR TREATING DUCHENNE
TITLE OF INVENTION: MUSCULAR DYSTROPHY AND BECKER MUSCULAR DYSTROPHY
FILE REFERENCE: 084177.0121
CURRENT APPLICATION NUMBER: US/15/732,190
CURRENT FILING DATE: 2017-09-29
PRIOR APPLICATION NUMBER: US 62/141,833
PRIOR FILING DATE: 2015-04-01
PRIOR APPLICATION NUMBER: US 62/310,479
PRIOR FILING DATE: 2016-03-18
NUMBER OF SEQ ID NOS: 826649
SEQ ID NO 132602
LENGTH: 23
TYPE: DNA
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic
Query Match 100.0%; Score 23; Length 23;
Best Local Similarity 100.0%;
Matches 23; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GCUGCCUCAGCCUCCCAAGUAGC 23
|||||||||||||||||||||||
Db 1 GCUGCCUCAGCCUCCCAAGUAGC 23
RESULT 2
US-15-732-190-158480
Sequence 158480, US/15732190
Publication No. US20190048337A1
GENERAL INFORMATION
APPLICANT: EDITAS MEDICINE
APPLICANT: HSU, Patrick David
APPLICANT: MAEDER, Morgan Lee
APPLICANT: ODONNELL, Penrose
APPLICANT: TYCKO, Joshua C.
APPLICANT: HUSTON, Nicholas C.
TITLE OF INVENTION: CRISPR/CAS-RELATED METHODS AND COMPOSITIONS FOR TREATING DUCHENNE
TITLE OF INVENTION: MUSCULAR DYSTROPHY AND BECKER MUSCULAR DYSTROPHY
FILE REFERENCE: 084177.0121
CURRENT APPLICATION NUMBER: US/15/732,190
CURRENT FILING DATE: 2017-09-29
PRIOR APPLICATION NUMBER: US 62/141,833
PRIOR FILING DATE: 2015-04-01
PRIOR APPLICATION NUMBER: US 62/310,479
PRIOR FILING DATE: 2016-03-18
NUMBER OF SEQ ID NOS: 826649
SEQ ID NO 158480
LENGTH: 24
TYPE: DNA
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic
Query Match 100.0%; Score 23; Length 24;
Best Local Similarity 100.0%;
Matches 23; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GCUGCCUCAGCCUCCCAAGUAGC 23
|||||||||||||||||||||||
Db 2 GCUGCCUCAGCCUCCCAAGUAGC 24
Therefore, the sequence set forth in instant Application’s SEQ ID NO: 99 is known and published, and present 100% identity with sequences set forth in Hsu’s SEQ ID Nos: 132,602 and 158,480.
The sequences are not described as “RNA spacer sequence” but as gRNAs comprising a “targeting domain”.
Instant’s Specification describes “a spacer sequence” as follow: “The natural CRISPR Cas9 system contains two RNAs, one is called the crRNA and contains sequences called spacer (assigns its targeting specificity) direct repeat (helps it bind with tracrRNA and Cas9) and a tracrRNA which contains a region complementary to the
crRNA direct repeat and anneals to the crRNA direct repeat sequence such that they form a dsRNA that binds to Cas9.” (see [0054]).
Hsu describes a first RNA comprising a targeting domain and a complementary domain and a second RNA with a second complementary domain (see Fig.1A).
Therefore, since the structure of SEQ ID NO: 99 is 100% identical to the sequences SEQ ID Nos: 132,602 and 158,480 described in Hsu, Hsu anticipates elements of claim 1.
Hsu also teaches that the nucleic acid composition further comprises a nucleotide sequence that encodes a third gRNA molecule comprising a targeting domain that is complementary to a third target domain of the DMD gene, and that the targeting domains of can comprise nucleotide sequences set forth in SEQ ID Nos: 206-826,366 (see [0074]).
Hsu also teaches that the gRNA is comprised within a nucleic acid molecule, e.g., a vector, viral vector, adeno-associated virus vector (see [0076]).
Hsu also teaches vectors comprising DNA encoding for the Cas9 protein and gRNAs ( see [1147]-[1149]).
Regarding claims 2-5, Hsu teaches that the nucleic acid molecule can comprise a promoter (see [0086]-[0087]).
Hsu also teaches that useful promoters for gRNAs include T7, H1, EF-1a, 7SK, U6, U1, tRNA promoters and Muscle Creatine Kinase promoter ([0592], [0618]-[0619], [1124], [1130], [1255]).
Regarding claims 6, 8, 9 and 10, Hsu teaches vectors that are AAV vectors ( see [0076]-[0085], [1134], [1139]-[1144]). Hsu specifically teaches AAV9 vector (see [0076], [0175], [1139]-[1140]). Hsu teaches that in some embodiments, the AAV is a self-complementary AAV (scAAV) ([1142]).
Regarding claim 7, Hsu teaches that the viral vectors are defective and missing some viral sequences that are being replaced by an expression cassette. Hsu teaches that the missing viral functions can be supplied in trans by packaging cell line comprising plasmid encoding for Rep and Cap genes from AAV (see [1144].
Examiner interprets that the viral vectors comprising the expression cassette with the oligonucleotide of interest, lack rep and cap genes.
Regarding claim 11, Hsu teaches nanoparticle and exosome ([1147], [1150], [1181], see Table 4 ([1124])).
Claims 1-4 and 6-12 are rejected under 35 U.S.C. § 102(a)(2) as being anticipated by Kabadi (Kabadi, A. M. et al. US Patent No. 12,053,531 B2, dated August 6, 2024, benefitting from priority from US Application No. 17/748,495 filed May 19, 2022, and US Provisional Applications Nos. 62/247,484 filed 10/28/2016 and 62/324,064 filed 04/18/2016).
Regarding claim 1, a search of instant Application’s SEQ ID NO: 122 (Qy = Query) leads to the following result:
RESULT 2
US-17-748-495A-1295552
Sequence 1295552, US/17748495A
Patent No. 12053531
GENERAL INFORMATION
APPLICANT: Vertex Pharmaceuticals Incorporated
TITLE OF INVENTION: MATERIALS AND METHODS FOR TREATMENT OF DUCHENNE MUSCULAR
TITLE OF INVENTION: DYSTROPHY (DMD)
FILE REFERENCE: 01245-0021-01US
CURRENT APPLICATION NUMBER: US/17/748,495A
CURRENT FILING DATE: 2022-05-19
PRIOR APPLICATION NUMBER: US 15/763,328
PRIOR FILING DATE: 2016-03-26
PRIOR APPLICATION NUMBER: PCT/US2016/059386
PRIOR FILING DATE: 2016-10-28
PRIOR APPLICATION NUMBER: US 62/247,484
PRIOR FILING DATE: 2015-10-28
PRIOR APPLICATION NUMBER: US 62/324,064
PRIOR FILING DATE: 2016-04-18
NUMBER OF SEQ ID NOS: 1410475
SEQ ID NO 1295552
LENGTH: 22
TYPE: DNA
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: chemically synthesized
Query Match 91.3%; Score 21; Length 22;
Best Local Similarity 66.7%;
Matches 14; Conservative 7; Mismatches 0; Indels 0; Gaps 0;
Qy 2 AAUAUGCUCUAAACUAUAGUG 22
||:|:||:|:||||:|:||:|
Db 2 AATATGCTCTAAACTATAGTG 22
The alignment clearly shows a nucleic acid sequence of SEQ ID NO: 1,295,552 (Db = Database) from US Patent No. 12,053,531 B2, i.e., Kabadi, presenting 91.3% identity to a sequence encoding the RNA spacer sequence of instant SEQ ID NO: 122.
Kabadi teaches in “Brief Description of the sequence listing” section in column 10, lines 46-67, that SEQ ID Nos: 627,855-1,410,399 is a list of gRNA 20-24 bp spacer sequences for targeting the dystrophin gene with an Acidominoccoccus, a Lachnospiraceae, and a Franciscella Novicida Cpf1 endonuclease ( see column 10, lines 64-67).
Therefore, Kabadi teaches a nucleotide sequence encoding an RNA spacer comprising at least 90% identity to the sequence set forth in one of SEQ ID Nos: 93-184, i.e., SEQ ID NO: 122 specifically.
Regarding claim 2, Kabadi teaches the nucleic acid, being a vector comprising one or more transcription and/or translation control elements and further comprising a promoter sequence (see column 52, lines 39-67).
Regarding claims 3 and 4, Kabadi teaches the promoter can be U6 or H1 (see column 52, lines 59-62).
Regarding claim 6, Kabadi teaches an Adeno-associated virus comprising the nucleic acid (see column 8, lines 39-46).
Regarding claim 7, Kabadi teaches that rep and cap genes are separate (i.e., not in) the rAAV genome (see column 54, lines 55-59; column 55, lines 18-25).
Regarding claim 8, Kabadi teaches the virus is a rAAV (see column 54, lines 50-67; column 55, lines 18-25; lines 32-41).
Regarding claims 9 and 10, Kabadi teaches the virus can be of serotypes AAV-1, AAV-2, AAV-3, AAV-4, AAV-5, AAV-6, AAV-7, AAV-8, AAV-9, AAV-10, AAV-11, AAV-12, AAV-13 and AAV rh.74 (see column 54, lines 59-65; columns 55 and 56, Tables 3 and 4).
Regarding claim 11, Kabadi teaches lipid nanoparticles (LNP) as delivery vehicle for the nucleic acid (see column 8, lines 36-46; column 53, lines 26-34, lines 55-67; column 54, lines 1-23; column 74, lines 1-17).
Regarding claim 12, Kabadi teaches a composition comprising the nucleic acid and a pharmaceutically acceptable carrier ( see column 57, lines 39-67; column 58, lines 1-34).
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDRA G DACE DENITO whose telephone number is (703)756-4752. The examiner can normally be reached Monday-Friday, 8:30-5:00EST.
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/A.D./Examiner, Art Unit 1636
/NANCY J LEITH/Primary Examiner, Art Unit 1636
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