DETAILED ACTION
This Action is in response to the communication filed on 09/23/2025.
Claims 22-23, 25, 27-28, 38, 40, 42, 44-45, 49-56 are pending.
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 II (claims 22-23, 25, 27, 28, 49-56) and of the species type II CRISPR/Cas effector polypeptide, nucleotide sequence encoding a protein of interest, 18-helix bundle, in the reply filed on 09/23/2025 is acknowledged. It is noted that although applicant expressly indicated that the election was made without traverse, it was also asserted that it is Applicant’s position that t would not be unduly burdensome to perform a search on all of the claims together in the present application. In response, it is noted that the instant application is the national stage of an international application and unity of invention rules are applied. It is noted that search burden is not a used in determination of unity of invention between different categories of related inventions, such as in this case.
Claims 38, 40, 42, 44-45 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, and claim 51 is withdrawn from further consideration as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09/23/2025.
Claims 22-23, 25, 27, 28, 49-50, 52-56 are under consideration as they read on the elected subject matter.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 22-23, 25, 27, 28, 49, 53-56 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. 2018/0127787 (hereafter “Gurumurthy”, of record – IDS citation) in view of U.S. 2019/0240340 (hereafter “Fleming”, of record – IDS citation) and WO 2020/051507 (hereafter “Zhang”).
It is noted that claim 22 the only independent claim under consideration and all other claims under consideration are dependent claims.
Regarding claim 22, Gurumurthy teaches a composition comprising: a) a gene-editing polypeptide; and b) a single stranded donor DNA (ssDNA donor) that comprises in order from 5' to 3': i) a first homology arm; ii) a nucleotide sequence of interest and iii) a second homology arm (e.g., see paragraph [0007]; claims 15, 19, 20; etc.).
Regarding claims 49-50, Gurumurthy teaches that the composition can comprise a CRISPR/Cas effector polypeptide, including Cas9 as well as guide nucleic acid (e.g., see claim 7, [0077], etc.).
Gurumurthy does not teach that the ssDNA donor is comprised in a nanostructure wherein the nucleotide of interest of the ssDNA donor is hybridized to staple oligonucleotides such that the nucleotide of interest has a length of from about 5 nm to about 500nm as required by claim 22.
However, Fleming teaches cell-penetrating nucleic acid nanostructures for delivery into cells both in vitro and in vivo (e.g., see abstract). Fleming teaches that DNA origami is a method through which single-stranded DNA can be systematically folded into complex and molecularly defined two- and three-dimensional nanostructures using oligonucleotide hybridization and inter-strand cross-overs to dictate the final shape (see paragraph [0003]). Fleming teaches a nucleotide sequence of interest hybridized to staple oligonucleotides such that the nucleotide of interest is folded via the staple oligonucleotides such that the nucleotide sequence of interest has a length of in the range of about 5nm to about 500nm (see Figure 6 for visualization of the nanostructure and paragraph [0021] for description of the nanostructure of Figure 6). Specifically, Fleming teaches that Figure 6 provides that complete caDNAno design schematic which is a 24 helix bundle structure with a dimension of approximately 100 nm×14 nm without functionalization (see [0021]). Fleming teaches that the nanostructure bundle structure folds the ssDNA scaffold (thus compacting the ssDNA) and results in improved transfection of target cells (e.g., see [0003], [0021] [0027]).
Zhang teaches that CRISPR technology allows for precise, targeted gene editing technology that provides vastly improved versatility and fidelity, “However, full realization of the potential for CRISPR-mediated gene editing requires targeted, efficient nuclear delivery of intact RNPs consisting of Cas proteins and single guide RNA (sgRNA), particularly for difficult-to-transfect cells.” (See page 1, line 29 through page 2, line 16). Zhang also teaches, “Efficient delivery of proteins, protein complexes, and multicomponent cargo to cells and tissues remains a difficult problem. Problems include size, stability, and ratio of components in multicomponent systems. CRISPR is a prime example of such a multicomponent cargo… However, the delivery of RNPs to the nucleus remains challenging using conventional transfection techniques. At present, no delivery platform offers full control over RNP stoichiometry and programmed intracellular release.” (See page 2,line 32 through page 3, line 11). Zheng teaches nucleic acid assemblies for use in targeted delivery of cargo wherein the cargo can be CRISPR ribonucleoprotein (RNP) complex (e.g., see abstract; page 3, lines 27-29). Zheng teaches that small nucleic acid “staple sequences” can be used to form the folded nucleic acid assemblies (also referred to as “scaffolded origami” or “origami”) (e.g., see page 21, lines 11-15).
Regarding claims 23, 25, Gurumurthy does not teach the DNA nanostructure comprises a 24-helix bundle as required, or that the ssDNA donor comprising a single stranded region that does not comprise a hybridized staple oligonucleotide.
Regarding claim 23, Fleming also teaches that the DNA nanostructure comprises a 24-helix bundle (e.g., see [0015], Figure 6, etc.).
Regarding claim 25, Flaming also teaches that the ssDNA donor comprising a single stranded region that does not comprise a hybridized staple oligonucleotide as evidenced in Figure 6, Furthermore, paragraph [0020] teaches that the nanostructure comprises overhanging structures, including 158 extruding single stranded overhangs.
Regarding claim 27, it is noted that the DNA bundle nanostructure taught by Fleming constitutes a virus-like particle, given the broadest reasonable interpretation,
Regarding claim 28, Fleming teaches that the DNA nanostructure an comprise a nucleic acid, such as an siRNA, within the DNA nanostructure (e.g., see [0020]).
Regarding claims 52-56, it is noted that “ about 10 nm” or “about 25 nm” and “about 50nm” is taught by Fleming (e.g., see [0021]), and further teaches that the DNA scaffold (which corresponds to the nucleotide of interest in Gurumurthy can be in the range of “about 2000-5000 nt in length” which includes “about 2500 nt in length”, given the broadest reasonable interpretation of “about” (e.g., see 0020]).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the date the claimed invention was filed to apply the DNA origami nanostructure of Fleming (which uses staple oligonucleotides to form a DNA nanostructure) to the ssDNA of interest taught by Gurumurthy and arrive at the claimed invention (including a 24-helix DNA bundle nanostructure, etc.) with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to apply the DNA origami nanostructure system in order to improve delivery of the composition comprising the DNA nanostructure. The positive results demonstrated by Fleming provides a reasonable expectation of success.
Therefore, the invention of the instant claims is prima facie obvious over Gurumurthy in view of Fleming and Zhang.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to J. E. Angell whose telephone number is (571)272-0756. The examiner can normally be reached Monday-Friday (8:30-5:00).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jennifer Dunston can be reached at (571) 272-2916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
J. E. Angell
Primary Examiner
Art Unit 1637
/J. E. ANGELL/ Primary Examiner, Art Unit 1637