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 .
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-2, 5-6, 23, 38-43, 62-63, 65, and newly filed 83-84) in the reply filed on December 17, 2025 is acknowledged.
Applicants also amended claims 62-63 and 70 and canceled claims 71 and 73. Claims 47-48, 61, and 69-70 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 December 17, 2025.
Applicants also elected SEQ ID NO: 2 (Type VI-D CRISPR-Cas effector protein); SEQ ID NO: 81 (accessory protein); and SEQ ID NO: 153 (direct repeat) without traverse.
Claims 1-2, 5-6, 23, 38-43, 62-63, 65, and 83-84 are under examination.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of 35 U.S.C. 112 (pre-AIA ). See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
Regarding claims 1-2, 5-6, 23, 38-43, 62-63, 65, and 83-84, the disclosure of the prior-filed application, U.S. Provisional Patent Application No. 62/527,957 fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112 (pre-AIA ), first paragraph for one or more claims of this application. These applications fail to provide support for the claims under examination, since there is no disclosure therein of a Type VI-D CRISPR-Cas effector protein having a sequence provided in Table 2. Although the application discloses CRISPR protein families formed around a WYL domain, the application does not disclose the claimed Type VI-D CRISPR-Cas effector proteins or their sequences. Thus, the priority date of claims 1-2, 5-6, 23, 38-43, 62-63, 65, and 83-84 is deemed to be the filing date of U.S. Provisional Patent Application No. 62/572,367, filed October 13, 2017.
Information Disclosure Statement
The Information Disclosure Statements filed March 23, 2020; November 18, 2020; and December 17, 2025 have been considered.
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, they have not been considered.
Specification
The use of the term HISTRAP at page 166, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
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.
The disclosure is objected to because of the following informalities:
At page 3, line 22, “HEPN” should be changed to “higher eukaryotes and prokaryotes nucleotide-binding domain (HEPN).”
Appropriate correction is required.
Claim Objections
Claims 5 and 23 are objected to because of the following informalities:
At claim 5, line 11, it is believed that “(RHH)” should be changed to “(RRH)” to reflect the “ribbon-ribbon-helix” recitation in the claim.
At claim 23, line 4, “HEPN” should be changed to “higher eukaryotes and prokaryotes nucleotide-binding domain (HEPN).”
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 1-2, 6, 23, 38-43, 62-63, 65, and 83-84 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.
Claim 1, line 7, recites an amino acid sequence provided in Table 2, which is improper. MPEP 2173.05(s) states "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." Applicants can overcome this rejection by listing the specific SEQ ID NOS: listed in Table 2.
Claims 2, 23, 38-43, 62-63, 65, and 83-84 depend from claim 1, and are therefore included in this rejection.
Claim 6, line 9, recites an amino acid sequence provided in Tables 4, 5, and 6, which is improper. MPEP 2173.05(s) states "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." Applicants can overcome this rejection by listing the specific SEQ ID NOS: listed in Tables 4, 5, and 6.
Claim 23, line 7, recites an amino acid sequence provided in Table 3, which is improper. MPEP 2173.05(s) states "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." Applicants can overcome this rejection by listing the specific SEQ ID NOS: listed in Table 3.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 5-6, 23, 38, 41, and 83-84 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more.
The claims recite a CRISPR-Cas system comprising an RNA guide or nucleic acid encoding the RNA guide and a Type VI-D CRISPR-Cas effector protein or nucleic acid encoding the effector protein, having a sequence having at least 85% sequence identity to an amino acid sequence provided in Table 2. The claims further recited that the system has an accessory protein having a WYL domain having a sequence having at least 85% sequence identity to an amino acid sequence provided in Tables 4, 5, or 6. The claims also recite that the effector protein has at least two HEPN domains and a direct repeat sequence, which has a nucleotide sequence provided in Table 3. The claims recite a cell comprising the CRISPR-Cas system, which encompasses prokaryotic cells from which such systems can be isolated.
This judicial exception is not integrated into a practical application because such CRISPR-Cas polypeptides and systems exist in nature, and can be isolated from a variety of bacterial species. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because, whether isolated or not, such naturally-occurring polypeptides are deemed to fall under the judicial exception of natural products, and as such, are not patent-eligible subject matter pursuant to the Supreme Court decision in Association for Molecular Pathology v. Myriad Genetics, Inc., -- U.S. -- (June 13, 2013).
This judicial exception is not integrated into a practical application because the system comprising a Cas polypeptide comprising a WYL domain, accessory proteins, HEPN domains, and direct repeat sequences, as well as nucleic acid components that form a complex with the Cas polypeptide is deemed to be a product of nature. The claims do not include additional elements that are sufficient to amount to the CRISPR-Cas composition being markedly different than the judicial exception because the claims do not include additional elements, when considered separately and in combination, that are sufficient to be markedly different than the judicial exception.
Subject Matter Eligibility Test for Products and Processes
Step 1 - Is the Claim to a Process, Machine, Manufacture or Composition of Matter? YES.
The claims provide for a composition comprising a Type VI-D Cas polypeptide having an amino acid sequence having 85% identity to an amino acid sequence provided in Table 2 and one or more nucleic acid components that form a complex with the Cas polypeptide and which is capable of directing sequence-specific binding of the complex to a target sequence of a polynucleotide (claim 1). The claims further provide for the Cas polypeptide having a WYL domain (claim 5). The claims provide for the complex being capable of directing cleavage at the target site of the polynucleotide (claims 5-6). The claims provide for an accessory protein having at least 85% sequence identity to an amino acid sequence provided in Tables 4, 5, or 6 (claim 6). The claims provide for a system where the effector protein comprises at least two HEPN domain an a direct repeat sequence having an nucleotide sequence provided in Table 3. Thus, the claims are directed to a statutory category (e.g., a product of nature).
Step 2A, Prong One — Does the Claim Recite an Product of Nature? YES.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because, whether isolated or not, such naturally-occurring Cas polypeptides and nucleic acid components are deemed to fall under the judicial exception of natural products, and as such, are not patent-eligible subject matter pursuant to the Supreme Court decision in Association for Molecular Pathology v. Myriad Genetics, Inc., -- U.S. -- (June 13, 2013).
In Myriad, the Supreme Court considered the patent eligibility of several claims directed to isolated DNA related to the human BRCA1 and BRCA2 cancer susceptibility genes. The Supreme Court held that certain of Myriad Genetics' claims to isolated DNA are not patent-eligible, because they read on isolated naturally-occurring DNA that is a "product of nature." The Court held that isolating a "gene from its surrounding genetic material is not an act of invention." The Supreme Court held that other claims are patent eligible, because they are limited to cDNA, which is a type of man-made DNA composition that is not naturally occurring. The Court held that "cDNA is not a 'product of nature' and is patent eligible under §101.”
Step 2A, Prong Two — Does the Claim Recite an Additional Elements that Integrate the Judicial Exception into a Practical Application? NO.
The Supreme Court has long distinguished between principles themselves, which are not patent eligible, and the integration of those principles into practical applications, which are patent eligible. However, absent are any additional elements recited in the claim beyond the judicial exceptions which integrate the exception into a practical application of the exception. The “integration into a practical application” requires an additional element or a combination of additional elements in the claim to apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception, such that it is more than a drafting effort designed to monopolize the exception. The claim limitations “a system comprising ,” “an RNA guide or nucleic acid encoding the RNA guide having a direct repeat sequence,” and “a Type VI-D Cas effector protein having an amino acid sequence having at least 85% identity to an amino acid sequence provided in Table 2,” and “is capable binding to the RNA guide and of targeting the target nucleic acid sequence complementary to the RNA guide spacer sequence” are not indicative of integration into a practical application. The above claim limitations are considered simply as the recitation of a naturally-occurring product. Thus, the claims do not provide for any element/step that integrates the law of nature into a practical application.
Step 2B - Does the Claim Recite Additional Elements that Amount to Significantly More than the Judicial Exception? NO.
The Supreme Court has identified a number of considerations for determining whether a claim with additional elements amounts to “significantly more” than the judicial exception(s) itself. The claims as a whole are analyzed to determine whether any additional element/step, or combination of additional elements/steps, in addition to the identified judicial exception(s) is sufficient to ensure that the claim amounts to “significantly more” than the exception(s).
However, the additional elements of the instant application, individually and in combination, do not amount to “significantly more” or “markedly different.” Under the Step 2B analysis, the “physical” elements of the claims are considered to be the same as those found in nature. For example,
For example, naturally occurring CRISPR Type I, II, and III enzymes each have different structures and function in different pathways (Sorek et al., 82 Annual Review of Biochemistry 237-266 (2013), and cited in the Information Disclosure Statement filed April 30, 2021). Additional naturally occurring CRISPR systems, which also have different structures and function in yet different pathways are also known (Koonin et al., 37 Current Opinion in Microbiology 67-78 (2017), and cited in the Information Disclosure Statement filed April 30, 2021).
Further, the specification itself notes that the CRISPR-Cas effector protein is RspCas13d (SEQ ID NO: 2) or EsCas13d (SEQ ID NO: 1) (page 12, first full paragraph and page 23, first full paragraph). These sequences are isolated from Ruminococcus sp. N15 and Eubacterium siraeum DSM 15702, respectively (see Table 2). Thus, the claimed Type VI-D CRISPR-Cas effector proteins and associated guides are deemed to be products of nature. In addition, Ruminococcus is known to have the sequence of SEQ ID NO: 81 (RspWLY1) (page 9, final full paragraph).
Therefore, the claimed systems comprising a Type VI-D CRISPR-Cas polypeptide having a sequence having at least 85% identity with an amino acid sequence provided in Table 2 and a guide RNA, capable of sequence-specific binding of the complex to a target sequence of a polynucleotide; having a WYL domain; an accessory protein having at least 85% sequence identity to an amino acid sequence provided in Tables 4, 5, or 6; at least two HEPN domain an a direct repeat sequence having an nucleotide sequence provided in Table 3 is not deemed to be markedly different than a Type VI-D CRISPR-Cas polypeptide and nucleic acid components found in nature. Simply noting that the composition comprises a Cas polypeptide and nucleic acid components, is not sufficient to distinguish the claimed Cas polypeptide compositions from naturally occurring Cas polypeptide compositions comprising such polypeptides and nucleic acid components.
Thus, when viewed both individually and as an ordered combination, the claimed elements, in addition to the identified judicial exception are found insufficient to supply an inventive concept because the elements are not deemed to be markedly different from those found in nature. Accordingly, the claims do not qualify as patent-eligible subject matter.
Section 33(a) of the America Invents Act reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
Claims 41-43 are rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. 101).
The claims recites a cell comprising a CRISPR-Cas system comprising an RNA guide or nucleic acid encoding the guide and a Type VI-D CRISPR-Cas effector protein having an amino acid sequence having at least 85% sequence identity to an amino acid sequence provided in Table 2. The cell can be a eukaryotic cell, such as a mammalian cell.
The instant specification provides that the cells can be human cells and/or be included in animal models (page 20, fifth paragraph). In addition, the claimed Type VI-D CRISPR-Cas system can be used for a variety of process, including mutagenesis, breeding, induction of cell dormancy, reduction of cell growth and/or cell proliferation, induction of cell anergy, induction of cell apoptosis, induction of cell necrosis, induction of cell death or induction of programmed cell death (page 22, first full paragraph). The instant specification discloses that polynucleotides encoding the Type VI-D CRISPR-Cas system can be introduced into a host cell and that the methods can be used to modify an RNA molecule by contacting a cell with the claimed system, which can be performed in vivo (page 22, first two full paragraphs). The specification further provides for treating diseases in a subject by targeting mutations that cause splicing defects and diseases, cancer, or infectious diseases (page 70, final two paragraphs to page 71, first full paragraph).
Thus, claims 41-43 are deemed to encompass human cells and tissues, which are present or intended to be present in a human organism, and which is non-statutory subject matter. As such the recitation of the limitation “isolated” cell would be remedial. See 1077 Off. Gaz. Pat. Office 24 (April 21, 1987).
Double Patenting
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 1-2, 23, 38-43, 62-63, 65, and 83 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-6, 8-10, 14, and 21-23 of U.S. Patent No. 10,392,616.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘616 patent and the instant application claim a CRISPR-Cas system.
Regarding claims 1-2 and 83, both the ‘616 patent and the instant application claim a CRISPR-Cas system comprising a guide RNA having a direct repeat sequence having a sequence provided in Table 3, which can be SEQ ID NO: 153 and a spacer sequence and a CRISPR-Cas effector protein having the sequence of SEQ ID NO: 2, which is an amino acid sequence listed in Table 2, and which is a Type VI-D CRISPR-Cas effector protein (claims 1, 8-10, and 14).
Regarding claim 23, both the ‘616 patent and the instant application claim that the Type VI-D CRISPR-Cas effector protein has at least two HEPN domains and the guide RNA has direct repeat sequence having at least 95% identid6 to SEQ ID NO: 153, which is a sequence provided in Table 3 (claims 2-3, 10, and 14).
Regarding claim 38, both the ‘616 patent and the instant application claim that the target is an RNA target (claim 22).
Regarding claims 39-40, both the ‘616 patent and the instant application claim a delivery system, which can be a nanoparticle, a liposome, an adeno-associated virus, and exosome, a microvesicle, or a gene-gun (claim 21).
Regarding claims 41-43, both the ‘616 patent and the instant application claim a cell comprising the Type VI-D CRISPR-Cas system (claim 23).
Regarding claims 62-63 and 65, both the ‘616 patent and the instant application claims a fusion protein where the CRISPR-Cas effector protein comprises a base-editing domain, an RNA methyltransferase, an RNA demethylase, a splicing modifier, a localization factor, or a translation modification factor (claims 5-6).
Therefore, the claims are not deemed to be patentably distinct.
Claims 1-2, 5-6, 23, 38-43, 62-63, 65, and 83-84 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5, 8-9, 11-12, 14, and 18-20 of U.S. Patent No. 11,168,322.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘322 patent and the instant application claim a CRISPR-Cas system.
Regarding claims 1-2 and 83, both the ‘322 patent and the instant application claim a CRISPR-Cas system comprising a guide RNA having a direct repeat sequence and a spacer sequence and a CRISPR-Cas effector protein having the sequence of SEQ ID NO: 2, which is an amino acid sequence listed in Table 2, and which is a Type VI-D CRISPR-Cas effector protein (claim 1).
Regarding claims 5-6, both the ‘322 patent and the instant application claim that the accessory protein has a WYL domain and has a sequence having at least 95% identity to SEQ ID NO: 81, which is a sequence provided in Table 4, which is interpreted as including the specific WYL domain (claims 8-9 and 11-12).
Regarding claim 23, both the ‘322 patent and the instant application claim a direct repeat sequence having at least 95% identid6 to SEQ ID NO: 153, which is a sequence provided in Table 3 (claims 2-3).
Regarding claim 38, both the ‘322 patent and the instant application claim that the target is an RNA target (claim 5).
Regarding claims 39-40, both the ‘322 patent and the instant application claim a delivery system, which can be a nanoparticle, a liposome, an adeno-associated virus, and exosome, a microvesicle, or a gene-gun (claims 18-19).
Regarding claims 41-43, both the ‘322 patent and the instant application claim a cell comprising the Type VI-D CRISPR-Cas system (claim 20).
Regarding claims 62-63 and 65, both the ‘322 patent and the instant application claims a fusion protein where the CRISPR-Cas effector protein comprises a base-editing domain, an RNA methyltransferase, an RNA demethylase, a splicing modifier, a localization factor, or a translation modification factor (claim 14).
Regarding claim 84, both the ‘322 patent and the instant application claim that the direct repeat sequence can have at least 95% identity to SEQ ID NO: 72 (claims 2-3).
Therefore, the claims are not deemed to be patentably distinct.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Hsu et al. (U.S. Patent No. 10,476,825, issued November 12, 2019, filed March 27, 2018, and claiming priority to U.S. Provisional Patent Application Nos. 62/548,846; 62/572,963; and 62/639,178; filed August 22, 2017; October 16, 2017; and March 6, 2018, respectively and PCT Patent Application No. WO 2019/040664, published February 28, 2019, filed August 22, 2018 and claiming priority to U.S. Patent Application No. 15/937,699 (U.S. Patent No. 10,467,825) and U.S. Provisional Patent Application Nos. 62/548,846; 62/572,963; and 62/639,178; filed August 22, 2017; October 16, 2017; and March 6, 2018, respectively, and cited in the Information Disclosure Statement filed December 17, 2025) disclose Cas13d (Type VI-D) CRISPR-Cas systems (abstract). However, both the ‘825 U.S. Patent and the ‘664 PCT Patent Application publication do not disclose or suggest a Cas13d CRISPR-Cas effector protein having the instantly claimed sequences. While the ‘825 U.S. Patent and the ‘664 PCT Patent Application publication disclose a Cas13d CRISPR-Cas effector protein having 98.7% similarity over a portion of the instantly claimed Type VI-D CRISPR-Cas effector protein, there is only a 57.6% similarity to the entire claimed Type VI-D CRISPR-Cas effector protein (see Appendix I).
Yan et al. (70(2) Molecular Cell 327-339 (2018), and cited in the Information Disclosure Statement filed March 23, 2020) disclose Type VI-D CRISPR-Cas effector protein systems isolated from Eubacterium siraeum (Es) and Ruminococcus sp. (Rsp) that are active in CRISPR RNA processing and target and collateral RNA cleavage (abstract). Yan et al. disclose that these CRISPR-Cas effector proteins have WYL domains (page 10).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NANCY J LEITH whose telephone number is (313)446-4874. The examiner can normally be reached Monday - Thursday 8:00 AM - 6:30 PM.
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NANCY J. LEITH
Primary Examiner
Art Unit 1636
/NANCY J LEITH/Primary Examiner, Art Unit 1636