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 .
Application Status
This action is written in response to applicant’s correspondence received on 11/10/2025. Claims 1-28 and 30 are pending. Claims 1, 3, 11-13, 22, 24, and 30 have been amended. Claim 29 has been cancelled. Claims 12-20, 23, 26-28, and 30 have been withdrawn as they are directed to a non-elected invention. Claims 1-11, 21-22, and 24-25 are currently under examination.
Any rejection of record in the previous office actions not addressed herein is withdrawn. New grounds of rejection are presented herein that were not necessitated by applicant’s amendment of the claims since the office action mailed 8/11/2025. Therefore, this action is not final.
Election of Species/Restriction
The Applicant’s election filed 7/16/2025 is acknowledged. The Applicant has elected Invention Group I, which encompasses claims 1-11, 21, 22, 24, and 25. The Applicant has further elected the species of SEQ ID NO 4628 and macular dystrophies or degeneration, including AMD. The election has been made without traverse.
With regards to the election of species, SEQ ID NO 4628 was searched and found to be free of the art. Thus, the search has been widened to another species recited in the independent claim: SEQ ID NO 5262. Note that not all recited sequences in claim 1 have been searched, and that presently only SEQ ID NOs 4628 and 5262 have been searched, as prior art has been found which reads on SEQ ID NO 5262. This is in accordance with MPEP 803.02, subsection III C2, which states that if an elected species is free of the art, the examiner shall extend the search to additional species in the claim but is not required to search all species. See MPEP 803.02, section III C2.
Furthermore, note that the 112(a) rejections are made with the election of SEQ ID NO 4628 in mind. Furthermore, it appears that the rationale applied to the 112(a) rejection can be applied to each of the recited sequences in the claims.
Track One Status
The Applicant’s Track One request mailed 12/02/2024 has been considered and granted on 3/10/2025.
Claim Objections
Claim 24 is objected to for the following minor informalities:
Regarding claim 24, claim 24 recites “a disease associated RNA splicing” which should be amended to read “a disease associated with RNA splicing.”
Appropriate action is required.
Drawings
The drawings are objected to because the figures are not properly labeled.
37 CFR 1.84 (u)(1) states “The different views must be numbered in consecutive Arabic numerals, starting with 1, independent of the numbering of the sheets and, if possible, in the order in which they appear on the drawing sheet(s). Partial views intended to form one complete view, on one or several sheets, must be identified by the same number followed by a capital letter. View numbers must be preceded by the abbreviation "FIG." Where only a single view is used in an application to illustrate the claimed invention, it must not be numbered and the abbreviation "FIG." must not appear.”
The drawings are objected to because Figure 19 is improperly labeled. Figure 19 contains partial views on separate sheets. For example, Figure 19 spans three separate sheets and is labeled “Fig. 19” and “Fig. 19 (cont’d)” but should be labeled “Fig. 19A” “Fig. 19B,” and “Fig. 19C “.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 102 – New Rejection not Necessitated by Amendment
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)(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, 21-22, and 24-25 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Zhang 2 (WO 2020/028555 A2, published 2/6/2020 with US designation and filing date 7/31/2019).
As an initial matter, Zhang 2 is a WIPO publication with US designation and an earlier effective filing date compared with the present application. Further, Zhang 2 lists different inventors and an additional applicant; Zhang 2 is therefore prior art.
Regarding claims 1-2, Zhang 2 teaches SEQ ID NO: 274 in paragraph 1159 as a Cas13 protein, which is 100% identical to SEQ ID NO: 5262 as shown in the alignment below:
PNG
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848
708
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Greyscale
Zhang 2 teaches that the Cas13 protein can be complexed with a guide RNA to bind to a target (e.g., paragraph 280). Zhang 2 teaches that the guide RNAs for such Cas13b proteins can be heterologous (e.g., paragraphs 222, 1166, and throughout).
Regarding claims 3-4, Zhang 2 teaches mutating the HEPN domain such that cleavage activity is reduced relative to wildtype and/or is catalytically inactive (e.g., paragraph 279).
Regarding claims 5-7, Zhang 2 teaches that the Cas protein can be fused with a functional domain such as an adenosine deaminase (paragraph 521).
Regarding claims 8-9, Zhang 2 teaches that the elements of their compositions, including the Cas protein, may be encoded into a polynucleotide such as a vector (paragraph 243).
Regarding claim 10, Zhang 2 teaches that the delivery of the Cas protein/composition may be in the form of mRNA (e.g., paragraph 675).
Regarding claim 11, Zhang 2 teaches that the delivery vehicle can be a lipid nanoparticle (paragraph 674) or an AAV (e.g., paragraph 1018).
Regarding claim 21, Zhang 2 teaches a method of cleaving a target RNA, comprising contacting the target RNA with the composition of claim 1, where a Cas/gRNA complex form to cleave a target (e.g., Example 12, Figure 71, and claim 372).
Regarding claim 22, Zhang 2 teaches mutating the HEPN domain such that cleavage activity is reduced relative to wildtype and/or is catalytically inactive (e.g., paragraph 279, Example 12).
Regarding claim 24, Zhang 2 teaches therapeutics using their compositions, where furthermore such therapies are directed to diseases associated with RNA splicing (e.g., paragraphs 799-804, specifically paragraphs 799 and 804, paragraphs 1016 and 976).
Regarding claim 25, Zhang 2 teaches the use of their composition for treatment of disease (e.g., paragraph 976) to include eye diseases (paragraph 977), where such an eye disease can be age-related macular degeneration (paragraph 991).
103 Rejection – Withdrawn
The Applicant’s arguments regarding the 103 rejection mailed 8/11/2025 have been reviewed and are persuasive. The Applicant argues that the CDD domain was created after the filing date of GenPept (of record). The use of GenPept as prior art was originally predicated on the publication of Accession number RKY08123, given as 10/15/2018. However, the Applicant points out that the CDD annotation of this protein as a Cas13 was not created until 1/8/2020, which post-dates the present filing date. The error was made as a result of a lack of revision history of RKY08123 within the NCBI database, where only one version of RKY08123 exists in the NCBI database that was uploaded on 10/15/2018. As such, the original 103 rejection was made under the assumption that all of the information contained in GenPept for accession number RKY08123 was present on the date 10/15/2018 (absent any revision or new versions of RKY08123, per NCBI BLAST). Thus, the teaching in GenPept which identifies the sequence as a Cas13 does not appear to be valid art. There does not appear to be a reason to combine a heterologous guide RNA with the recited sequence of 5262 based upon guidance of GenPept. However, as discussed in the new 102 rejection based on Zhang 2, SEQ ID NO: 5262 in combination with a heterologous gRNA does not appear to be free of the art as it is anticipated by Zhang 2 (see 102 rejection, above).
Claim Rejections - 35 USC § 112 – New Rejection Necessitated by Amendment
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 24-25 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.
MPEP 2163.II.A.3.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”.
For claims drawn to a genus, MPEP § 2163 states the written description requirement for a claimed genus may be satisfied 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 Regents of the University of California v. Eli Lilly & Co, 119 F.3d at 1568, 43 USPQ2d at 1406.
Regarding claim 24, claim 24 recites a method of treating a disease associated with RNA splicing, transport, localization, translation, and/or turnover, comprising administering a composition of claim 1, where the composition modulates splicing, transport, localization, translation, and/or turnover associated with the disease. Claim 24 therefore recites the claim limitation of claim 1, where claim 1 recites a composition comprising a Cas protein which forms a complex with a gRNA which directs the complex to a target sequence. Claim 24 therefore broadly recites “target sequences,” where furthermore the claim recites that a disease is treated by the administering of the composition of claim 1, which requires a “target” to be bound by the complex of claim 1. Claim 24 therefore broadly recites the genus of “target sequence” which can be targeted to affect a change/treatment in a disease associated with, for instance, DNA splicing. As discussed further below, the Applicant was not in possession of the broad genus of such targets as those recited with the specific function of treating a disease associated with RNA splicing because, as it was known in the art at the time of filing, RNA splicing variants and targets associated with diseases were known to be an unpredictable genus.
With regards to the specification, the Applicant has not shown possession of the claimed subject matter. The Applicant has classified and characterized a few Cas enzymes and reduced their functionality to practice. For instance, the Applicant recites Example 4 and demonstrated that the smaller Cas proteins identified can act as RNA base editors (paragraphs 1265-1274). The Applicant has reduced to practice such methods in HEK293 reporter constructs (paragraph 1269). The Applicant has not taught and reduced to practice specific targets using their methods for diseases such as cancer and AMD (as recited in claim 25). The Applicant recites RNA knockdown and editing assays (e.g., paragraphs 1299-1304). The Applicant also offers Table 10 which includes a list of diseases and genes associated with said diseases which could potentially be targeted by their systems (Table 10, paragraph 962).
However, with regards to the state-of-the-art, it is known that targets for diseases associated with RNA splicing are complex and unpredictable. For instance, Truty (Truty R et al. Am J Hum Genet. 2021 Apr 1;108(4):696-708) is a research article which focuses on RNA splicing variants and their association with disease (Title, Abstract, and throughout). Truty teaches that:
“The complexities of gene expression pose challenges for the clinical interpretation of splicing variants. To better understand splicing variants and their contribution to hereditary disease, we evaluated their prevalence, clinical classifications, and associations with diseases, inheritance, and functional characteristics in a 689,321-person clinical cohort and two large public datasets. In the clinical cohort, splicing variants represented 13% of all variants classified as pathogenic (P), likely pathogenic (LP), or variants of uncertain significance (VUSs). Most splicing variants were outside essential splice sites and were classified as VUSs,” (Abstract).
Truty further teaches that natural variations of splicing confound the clinical relevance of splice variants (Abstract).
Truty teaches that:
“Variants that may alter RNA splicing can be computationally predicted, and these predictions can be confirmed by RNA analysis. However, assessing the clinical consequences of abnormal splicing can be challenging because of an incomplete understanding of alternative splicing and normal RNA expression profiles across tissues. Some studies have revealed previously unrecognized variety in RNA transcript isoforms associated with well-studied genes, including BRCA1 and BRCA2, showing that our understanding of naturally occurring alternative splicing of disease gene transcripts is still evolving. Recent studies have also illuminated how differential expression of transcript isoforms can influence whether certain sequence variants are tolerated. As a result of this underappreciated complexity, variants that allow biologically viable alternative
splicing may be incorrectly classified as disease causing. Therefore, investigating both the spectrum of variants predicted or assumed to cause abnormal splicing
across a broad variety of genes and their contribution to naturally existing genomic variation is essential to understanding their overall involvement in hereditary disease,” (Introduction, first paragraph).
Thus, Truty teaches that there is known unpredictability when attempting to define RNA splicing associated with diseases, where large cohort models and direct RNA analysis is required in order to help clinical interpretation (Abstract, and Introduction).
Truty further teaches that:
“Several computational tools are used to predict the potential splicing effects of variants encountered during clinical genetic testing for hereditary disease. However, these tools often do not have a high positive predictive
value when used individually, particularly for variants outside the essential splice site(s) (ESS). Therefore, their predictions are often not considered usable evidence for variant interpretation unless there is consensus among them,” (Introduction, first paragraph).
Truty therefore teaches that prediction methods for the effects of RNA splice variants and their clinical roles are unpredictable, where Truty further teaches that previously identified variants with unknown significance can be classified as pathogenic splice variants or benign based upon further analysis (Introduction, first paragraph, final sentence).
Truty further teaches that:
“Furthermore, the challenge of interpreting splicing variants is not limited to hereditary cancer and has been noted in other disease areas, such as inherited retinal diseases. To avoid negative outcomes, it is essential to consider a variety of types of evidence for variant interpretation and to use appropriate control samples during RNA analysis. Compounding the challenge of accurately interpreting the effects of a splicing variant is the conundrum of defining which one or a subset of transcript isoforms may be affected. This has implications for identifying molecular etiologies of disease through genetic testing because clinical laboratories may sometimes choose a single reference transcript when reporting observed variants. In some cases, the chosen reference transcript may not be fully relevant to the disease in question (and the prediction of splicing effects can be dependent on the transcript chosen), leading to missed diagnoses. It is expected that clinical interpretation of variants identified during genetic testing for inherited disease will eventually consider the individual expression patterns of specific transcripts for each disease gene and how those patterns may affect the manifestation of disease. Various studies have shed light on the complexity of gene expression through discovery of novel exons, complex interactions between splicing variants and tissue-specific effects, the effect of cellular context on splicing in the absence of variants that affect splicing (e.g., in the progeria-related LMNA gene [MIM:150330]), and quantitative effects of transcript isoforms on clinical phenotypes,” (page 704, left column, paragraphs 1-2).
Truty therefore teaches that RNA splice variants and their exact roles in diseases – including cancer and retinal diseases such as those recited in instant claim 25 – are complex and undefined. Given that such uncertainty and complexity exists concerning the classification and roles of specific RNA splice variants in disease, the effects of targeting such an RNA in the context of a given disease are also unpredictable. The Applicant was therefore not in possession of the genus “target sequence” as recited in claim 1 and by extension claim 24 and 25, as such a genus is unpredictable and uncharacterized. Furthermore, the teachings of Truty generally teach that the genus of target in the context of what such a target would be in order to act as a treatment in the context of disease is largely undefined (see specific passages quoted above, and throughout Truty). In short, the genus of “target” in the context of DNA-splicing associated disease is known to be uncharacterized; the Applicant has not characterized this genus or defined and recited specific targets commensurate in scope with what is claimed.
112(a) Rejection – Partially Withdrawn
The Applicant has amended the claims to significantly narrow their scope from sequences comprising 90% identity to newly recited 98% identity. The Applicant argues that they have characterized the recited proteins and domains to a degree sufficient to show possession of the claimed genus of sequences. These arguments are persuasive. The Applicant’s amendments have caused reconsideration of the claims, and a new 112(a) rejection (above).
Double Patenting – Maintained/Updated with New Rejection
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-11, 21-22, and 24-25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 7, 9, 11, 12-15, 18, and 20 of copending Application No. 18/965,675 (‘675, reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claim 1, claim 1 of ‘675 recites a Type VI Cas protein comprising an amino acid sequence of SEQ ID NO: 274, and a guide sequence capable of forming a complex with the Cas protein and directing the complex to bind to a target sequence. SEQ ID NO: 274 recited in ‘675 is identical to instantly recited SEQ ID NO: 5262. Thus, both of claims 1 in ‘675 and the instant application recite the same subject matter.
Regarding claim 2, claim 2 of ‘675 recites the Cas protein is SEQ ID NO: 274, and therefore recites the same subject matter as instant claim 2.
Regarding claim 3, claim 3 of ‘675 recites the Cas protein comprises one or more mutations in a HEPN domain to reduce collateral activity.
Regarding claim 4, claim 4 of ‘675 recites the Cas protein comprises one or more mutations in HEPN to render the Cas catalytically inactive.
Regarding claims 5-7, claim 1 of ‘675 recites that the Cas is associated with a functional domain that is an adenosine or cytidine deaminase.
Regarding claims 8-9, claim 9 of ‘675 recites that the elements can be encoded in a polynucleotide.
Regarding claim 10, claim 10 of ‘675 recites the polynucleotide is mRNA.
Regarding claim 11, claim 11 of ‘675 recites the delivery vehicle is a lipid nanoparticle.
Regarding claim 21, claim 21 of ‘675 recites the identical method of the presently claimed method.
Regarding claim 22, claim 22 of ‘675 recites the same limitations of instant claim 22.
Regarding claims 24-25, claims 24-25 of ‘675 recite the same limitations as the instantly recited claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 5-11, 21, and 24-25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 23, 37, 52, 58, 60, 69, and 87 of copending Application No. 17/761,272 (‘272, reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claims 1-2, claim 2 of ‘272 recites each of the SEQ ID NOs of the Cas enzymes recited in instant claim 1 (note that instant SEQ ID NO: 5873 of the instant application reads on SEQ ID NO: 4763 of ‘272, as recited in claim 2 of ‘272). Claim 1 of ‘272 recites that the Cas protein is in complex with a guide RNA to direct it to a target.
Regarding claims 5-7, claim 2 of ‘272 recites that the Cas can be associated with a functional domain such as adenosine deaminase.
Regarding claim 8, claim 52 of ‘272 recites that the components are encoded in polynucleotides.
Regarding claims 9-10, claim 23 of ‘272 recites that the Cas protein can be encoded in mRNA.
Regarding claim 11, claims 58 and 60 of ‘272 recite that the composition is in a delivery vehicle which is a lipid nanoparticle.
Regarding claim 21, claim 69 of ‘272 recites:
“A method of modifying one or more target sequences, the method comprising contacting the one or more target sequences with the composition of claim 1… wherein modifying the one or more target sequences comprises increasing or decreasing expression of the one or more target sequences.”
Furthermore claim 2 recites that the Cas protein cleaves a target.
Regarding claims 24-25, claim 87 of ‘272 recites treating a disease by
administering the composition of claim 1. Claim 37 of ‘272 recites remedying a mutation associated with disease, such as Marfan syndrome. A practitioner could thus immediately envision the limitations of instant claims 24-25 based on the teachings and recitation of the claims of ‘272.
Claims 3-4, and 22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 23, 52, 58, 60, 69 of copending Application No. 17/761,272 (‘272, reference application) as applied to claims 1-2, 5-11, and 21 above and further in view of Zhang (WO 2017/070605 A1, published 4/27/2017, of record). Although the claims at issue are not identical, they are not patentably distinct from each other.
A discussion of claims 1-2, 5-11, and 21 as they relate to ‘272 is given above and incorporated herein.
Regarding claims 3-4 and 22, ‘272 does not recite HEPN mutations rendering catalytically inactive or reduced collateral cleavage.
Regarding instant claims 3-4 and 22, Zhang teaches Cas13b in a complex with crRNA is activated upon binding to target RNA and subsequently cleaves any nearby ssRNA targets (i.e. "collateral" or "bystander" effects) (paragraph 304). Zhang teaches RNase activity depends on the presence of two HEPN domains (paragraph 248). Zhang teaches the effector protein may have reduced or abolished nuclease activity compared with an effector protein lacking said one or more mutations and the mutations are in one or more HEPN domains where such mutations are preferred embodiments of the invention (paragraph 74).
It would have been obvious to a person of ordinary skill in the art before the time of the effective filing date to modify the teachings of ‘272 with Zhang to arrive at Cas proteins with mutations in the HEPN domain to reduce collateral activity or render catalytically inactive Cas enzymes as taught by Zhang, as Zhang teaches that this is a known methodology to alter the functionality of Cas enzymes with desirable effects (above).
Response to Arguments
The arguments submitted 11/10/2025 have been considered but are not persuasive. Applicant requests that the double patenting rejection be held in abeyance. A request to hold a rejection in abeyance is not a proper response to a rejection. Rather, a request to hold a matter in abeyance may only be made in response to an OBJECTION or REQUIREMENTS AS TO FORM (see 37 CFR 1.111(b) and MPEP §714.02). Thus, the double patenting rejections of record have been maintained as no response to these rejections has been filled by applicant at this time.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DOUGLAS CHARLES RYAN whose telephone number is (571)272-8406. The examiner can normally be reached M-F 8AM - 5PM.
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, Ram Shukla can be reached at (571)-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/D.C.R./Examiner, Art Unit 1635
/KIMBERLY CHONG/Primary Examiner, Art Unit 1636