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 June 04, 2026.
Claims 1, 6-8, 12, 14, 16-18, 22-23, 29, 33, 42, 45, 50, 53-54, 57, 59-60, 70, and 72 are currently pending.
Claim 1 is directed to an allowable product. Pursuant to the procedures set forth in MPEP § 821.04(b), claim 18, is directed to the process of making or using the allowable product, previously withdrawn from consideration as a result of a restriction requirement, is hereby rejoined and fully examined for patentability under 37 CFR 1.104. Claims 42, 50, 53, 57, 59, 70, and 72 are directed to the invention(s) of Group II does not require all the limitations of an allowable product claim, and have NOT been rejoined.
Because a claimed invention previously withdrawn from consideration under 37 CFR 1.142 has been rejoined, the restriction requirement between groups I and II as set forth in the Office action mailed on 11/07/2025 is hereby withdrawn. In view of the withdrawal of the restriction requirement as to the rejoined inventions, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application.
Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Accordingly, claims 1, 6-8, 12, 14, 16-18, 22-23, 29, 33, 45, 54, and 60 are examined herein.
Any rejection or objection not reiterated herein has been overcome by amendment.
For clarity, rejections pertaining to independent claim 1 and its dependent claims are addressed separately from those pertaining to independent claim 22 and its dependent claims.
Priority
Acknowledgment is made of applicant's claim for priority based on a US Provisional Application
No. 63/105,177 filed on October 23, 2020.
Specification
The disclosure is objected to because of the following informalities: there are terms including "Applicantsidentifies" ([1035]) and "Applicantsobserved" ([1038]) where a space is missing between the two words. The Examiner recommends Applicant thoroughly review the specification to correct similar issues that may be present in additional paragraphs throughout the specification.
Appropriate correction is required.
The use of the terms “9° N™ DNA Ligase” and “SplintR®Ligase”, 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 following sections address rejections of claims 1, 6-8, 12, 16-18, and 33.
Withdrawn Claim Rejections - 35 USC § 101
The amendments to claim 1 has overcome the rejection of claims 1, 5-8, 12, 14, 16-17, and 33 under 35 USC 101 on the basis that the composition comprises an IscB polypeptide and a heterologous ωRNA molecule. The specification defines a heterologous ωRNA as “an ωRNA molecule that is not derived from the same species as the IscB polypeptide nuclease, or comprises a portion of the molecule, e.g., spacer, that is not derived from the same species as the IscB polypeptide nuclease” ([0152]). Accordingly, the claimed composition is produced by combining two nature-based products, but the markedly different characteristic analysis is applied to the resultant combination, rather than its component parts (see MPEP 2106.04(c)(I)(A)). Thus, the recitation of “a heterologous ωRNA molecule” and “wherein the ωRNA is capable of forming a complex with the IscB polypeptide and directing the IscB polypeptide to a target polynucleotide” refers to markedly different structural and functional characteristics than combination of naturally occurring IscB polypeptide and ωRNA molecule.
Withdrawn Claim Rejections - 35 USC § 112 – Written Description
The rejection of claim 1 and its dependent claims, under 35 USC 112 for failing to comply with the written description requirement has been withdrawn in view of amendments to claim 1 to recite that the IscB polypeptide comprises an N-terminal PLMP domain, narrowing the breadth of the claim. The specification discloses that the N-terminal PLMP domain is a conserved feature of the IscB family (FIG. 3), and truncation of more than four amino acids of the PLMP domain abolishes cleavage activity (FIG. 49, [01043]). Thus, the specification discloses a recognized correlation between structure and function of the PLMP domain and IscB protein.
Regarding claim 1, Applicant’s arguments, pg. 21, para. 3 and 4, have been fully considered and they are persuasive. The disclosure that 57 of 86 phylogenetically diverse IscB systems are active by identification of a target-adjacent motif sequence (Table 9; FIG. 48) directly demonstrates that the functional property of the IscB genus is conserved across representative members spanning multiple bacterial and archaeal lineages. In addition, the specification discloses that ωRNA molecules share high degrees of structural and sequence similarity, particularly in shared multi-stem regions and pseudoknots (FIG. 9g, FIG. 47A-B; [01039]. Accordingly, the specification discloses a recognized correlation between structure and function of ωRNA molecules to form a complex with the IscB polypeptide and directing the IscB polypeptide to a target polynucleotide.
The rejection of claim 12 for failing to comply with the written description requirement has been withdrawn in view of amendments to claim 12 to specify the functional domain from a closed enumerated list, narrowing the breadth of the claim. The specification defines each of the recited functional domain with a known biochemical activity ([0211]-[0213]). Further, the specification incorporated by reference working examples of CRISPR-Cas systems comprising instantly recited functional domains, wherein the Cas systems share structural homology to IscB ([0213]). Accordingly, the specification provides sufficient written description support for instant claim 12.
Withdrawn Double Patenting
The provisional statutory double patenting rejection (35 USC 101) of claims 1, 7-8, 16-17, and 33 over copending Application No. 18/712,779 has been withdrawn in view of amendments to claim 1 to recite that “an HNH domain inserted between the RuvC-II and RuvC-III subdomains” and that the ωRNA molecule is heterologous.
The instant application has an earlier filling date of 04/20/2023 relative to copending Application No. 18/712,779 (filling date of 05/23/2024) and 18/956,654 (filling date of 11/22/2024). Pursuant to MPEP 804(I)(B), where an application having an earlier effective filling date has only provisional nonstatutory double patenting rejections remaining, the provisional NSDP rejections should be withdrawn. As discussed above, the amendment filed and Applicant’s arguments obviates the rejections of record for claims 1, 6-8, 12, 16-17, and 33. Thus, the provisional NSDP rejections over copending Application No. 18/712,779 and 18/956,654 have been withdrawn.
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.
Claim 18 is 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 18 recites the limitation "wherein the polypeptide" in line 3. There is insufficient antecedent basis for this limitation in the claim. There is no prior recitation of a polypeptide. It is noted the first recitation of “an IscB polypeptide” is in claim 1. It is unclear how the requirement of an IscB polypeptide is related to the polypeptide in claim 18. It is unclear whether the polypeptide of claim 18 is required to be an IscB polypeptide.
Further, claim 18 recites the limitation “nucleic acid components” in line 3. There is no prior recitation of nucleic acid components in claim 1. It is unclear which element is being further defined in instant claim.
Allowable Subject Matter
Claim 1, 6-8, 12, 16-17, and 33 allowed.
The following is a statement of reasons for the indication of allowable subject matter: Claim 1 is drawn to a composition comprising an IscB polypeptide and a heterologous ωRNA molecular that is capable of forming a complex with the IscB polypeptide and directing the IscB polypeptide to a target polynucleotide. The claim further defines the IscB polypeptide to comprise specific structures including an N-terminal PLMP domain, which the specification discloses that it is a conserved feature of the IscB family (FIG. 3), and truncation of more than four amino acids of the PLMP domain abolishes cleavage activity (FIG. 49, [01043]). The IscB polypeptide also comprises a split Ruv-C nuclease domain comprising RuvC-I, RuvC-II, and RUvC-III subdomains, and an HNH domain inserted between the RuvC-II and RuvC-III subdomains. The working examples disclosed in the specification are discussed in previous Office Action mailed on March 06, 2026, page 21.
The closest prior art is Kapitonov et al (Journal of Bacteriology, 2016, 198(5):797-807) whose teachings were discussed in previous Office Action mailed on March 06, 2026. Specifically, Kapitonov et al teach that IscB proteins are the closest homologs of Cas9 that are not linked to CRISPR-Cas systems (pg. 804, right-column, second paragraph), and that IscB proteins might function analogously to Cas9 proteins (pg. 806). Thus, Kapitonov et al do not teach or suggest with reasonable expectation of success IscB proteins comprising instantly claimed structures and function to form a complex with a heterologous ωRNA molecule.
Claim 18 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
The following sections address rejections of claims 22-23, 25-27, 29, 45, 54, and 60.
Claim Objections
Claims 22 and 27 objected to because of the following informalities:
Claim 22, line 3, recites “the IscB polypeptide” which is inconsistent with “the IscB protein” in line 2. It is recommended to modify the term “polypeptide” to “protein” for claim language consistency. It is noted that independent claim 1 recites an IscB polypeptide whereas independent claim 22 recites an IscB protein. The Examiner recommends that Applicant thoroughly review all corresponding dependent claims for consistency.
Claim 22, line 2, there is an extra space between the words “comprises” and “one”.
Claim 27 recites wherein the IscB protein further comprises an HNH domain; further comprising a first and second nucleic acid molecule…. This recitation contains a grammar error. The Examiner is interpreting the IscB protein to comprise both an HNH domain and a first and second nucleic acid molecule. It would be remedial to add the recitation of “and” between the two recited limitations.
Appropriate correction is required.
Withdrawn Claim Rejections - 35 USC § 101
The rejection of claims 22-23, 25-27, 29, 45, 54, and 60 under 35 USC 101 has been withdrawn in view of amendments to claim 22 to recite that the IscB protein comprises “one or more nuclear localization signals (NLS)”. Applicant argues that “naturally occurring IscB protein do not contain an NLS” and that “nuclear targeting capacity is entirely absent from naturally occurring IscB, which exists only in prokaryotic cellular contexts” (pg. 18, para. 3). Applicant’s arguments have been fully considered and they are persuasive. The recitation of that the IscB protein comprises one or more NLS refers to a markedly different structural characteristic than naturally occurring IscB proteins.
Further, the rejection under 35 USC 101 has also been withdrawn in view of amendments to claim 22 to recite that the IscB protein is a chimeric polypeptide comprising at least one domain from a first IscB polypeptide and at least one domain from a second IscB polypeptide. The specification discloses that “a chimeric enzyme can comprise a first fragment and a second fragment, and the fragments can be of IscB polypeptide nuclease orthologs of organisms of a genus or of a species, e.g., the fragments are from IscB polypeptide nuclease orthologs of different species” ([0141]). Accordingly, the recitation that the IscB protein is a chimeric polypeptide refers to markedly different structure than naturally occurring IscB proteins.
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 23, 25, and 26 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 23 and 26 recites the limitation “wherein the X domain” in line 1. There is insufficient antecedent basis for this limitation in the claim. There is no prior recitation of X domain. Thus, it is unclear which element is being further defined in the instant claim.
Claims 23 recites “wherein the X domain has an amino acid sequence that share at least 50%...sequence identity with X domains in Table 2”, which renders the claims indefinite. 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. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted)." It is unclear which sequences in Table 2 are intended as the reference for determining 50% sequence identity given that not all sequences in Table 2 contain an X domain. The claims do not specify whether sequences lacking the X domain are excluded from comparison. Accordingly, a person of ordinary skill in the art would not be able to determine the scope of the claim with reasonable certainty.
Claim 25 recites “wherein the IscB protein shares at least 80%...sequence identity with a IscB protein selected from Tables 2 and 3”, which renders the claim indefinite. See MPEP 2173.05(s) citation above. It is unclear which specific features, domains, or combinations thereof define the scope of the claim. It is unclear whether the claim encompasses all entries in Tables 2 and 3, only certain embodiments in the tables, or any variants thereof. By reciting the relevant accession numbers, amino acid ranges, or domain compositions directly in the claim language would clearly identify which IscB sequences and structures are required.
Claim Rejections - 35 USC § 112 – Written Description
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 22-23, 26-27, 29, 45, 54, and 60 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”. MPEP § 2163 further states the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species.
Claim 22 is drawn to a composition comprising an IscB protein that comprises one or more nuclear localization signals (NLS). The breadth of the claim encompasses an enormous number of IscB proteins that are not defined by structure and/or function.
The specification fails to disclose complete or partial structure required to meet instant claim limitations, except the incorporation of one or more NLS. The specification discloses that IscB polypeptides may comprise a split RuvC nuclease domain, a NHN endonuclease domain, or both ([0121]). The IscB polypeptide also may comprise a C-terminal domain or a N-terminal PLMP domain ([0121]). It is unclear what is the structure required to be considered as an IscB protein. The specification fails to disclose identifying structural or functional characteristics that would allow one skilled in the art to recognize members within the claimed genus.
Regarding the state of the art, Kapitonov et al (Journal of Bacteriology, 2016, 198(5):797-807) teaches that K.tedonobacter racemifer naturally encodes IscB polypeptides, including IscB2 protein contains an HNH insertion within RuvC-like domain and an IscB1 protein that only contains a RuvC-like domain (pg. 799, left-column, second paragraph). Thus, the prior art teaches that IscB proteins are identifiable by different structures and one skilled in the art cannot predictably recognize members within the claimed genus merely by the presence of one of the many domains disclosed.
Further, dependent claims 23, 26-27, 29, 45, 54, and 60 do not recite any limitations that support the possession of any species of IscB protein recited in claim 22; Thus, dependent claims are also rejected for depending from a rejected claim and failing to remedy the lack of written description therein. Although claims 23 and 25 recite that the IscB protein comprises an X domain or shares sequence identity with IscB proteins selected from Tables 2 and 3, the lack of written description of claims 23 and 25 is discussed below.
Based on the preponderance of the evidence, including the relevant teachings of the specification, the absence of working examples, and lack of prior art on structure of IscB proteins, one skilled in the art would conclude that Applicant was not in possession of the claimed genus of any IscB proteins comprising one or more NLS.
Claim 22 is also drawn to a composition comprising an IscB protein that is a chimeric polypeptide comprising at least one domain form a first IscB polypeptide and at least one domain from a second IscB polypeptide. This claim is drawn to possession of any chimeric IscB protein that comprises at least two domains (any domain), each from a different IscB polypeptide. The breadth of claim 22 encompasses a genus defined solely by structure.
The specification defines “a chimeric enzyme can comprise a first fragment and a second fragment, and the fragments can be of IscB polypeptide nuclease orthologs of organisms of a genus or of a species, e.g., the fragments are from IscB polypeptide nuclease orthologs of different species” ([0141]). The specification discloses reduction to practice of two IscB proteins, OgeuIscB and AwaIscB, which are not chimeric IscB proteins as stated in Table 9 that both are derived from one single organism, specifically from metagenome genome assembly (Contig Accession OGEU01000025.1 and from Allochromatium warmingii (Contig Accession FNOW01000019.1), respectively. Even if they are both chimeric IscB proteins, disclosure of merely two examples are not representative members across the claimed genus. The specification teaches numerous types of domains, including a N-terminal X domain (FIG. 3, [0133]), Y domain (Table 2, [0261]), HNH domain ([0133], RuvC domain that may comprise multiple subdomains ([0128]-[0132]). Each of these domains have different structure and functions. Not only does the specification fail to provide guidance on how these domains can be mixed and matched to obtain chimeric IscB proteins, it also fails to provide guidance on how these domains from different species can be mixed and matched despite that they share structural and sequence similarity.
The state of the art does not teach any chimeric IscB proteins comprising the claimed structure.
Further, dependent claims 23, 26-27, 29, 45, 54, and 60 do not recite any limitations that support the possession of any species of IscB chimeric protein recited in claim 22; Thus, dependent claims are also rejected for depending from a rejected claim and failing to remedy the lack of written description therein.
Based on the preponderance of the evidence, including the relevant teachings of the specification, the absence of working examples, and lack of prior art on chimeric IscB proteins, one skilled in the art would conclude that Applicant was not in possession of the claimed genus of chimeric IscB proteins comprising the recited structure of claim 22.
Claim 23 is drawn to the composition of claim 22 wherein the X domain has an amino acid sequence that shares at least 50% sequence identity with X domains in Table 2. This claim encompasses a broad genus of X domains sharing only 50% sequence identity.
The specification teaches the X domain is characterized by a conserved PLMP four amino acid motif (FIG. 3, [0133]), which is a partial structure because all species of X domains identified in Table 2 comprises of more than 40 amino acids. The specification further teaches “truncation of more than 4 aa of the PLMP domain [X domain] of AwaIscB abolished cleavage activity (FIG. 49)” ([01043]), which indicates there is a correlation between structure and function; however, the recited AwaIscB protein is not included in Table 2. It is not clear whether this correlation applies to the IscB proteins in Table 2 as they contain X domains or it is applied to AwaIscB protein only. Nevertheless, the specification fails to disclose which residues within the remaining 50% of the X domain can be varied while retaining activity. Further, the X domains identified in Table 2 are limited to a small number of IscB proteins and are not representative species of the claimed genus. It is noted that Table 1 provides a comprehensive list of species for IscB protein but the X domains are not identified.
The state of the art does not teach any knowledge of an N-terminal X domain in IscB proteins, supported by the specification that this domain was previously unidentified and lacks clear homology to known domains and is absent in Cas9 ([01035]).
Based on the preponderance of the evidence, including the relevant teachings of the specification, the absence of working examples, and lack of prior art on IscB proteins comprising N-terminal X domain, one skilled in the art would conclude that Applicant was not in possession of the claimed genus of IscB proteins wherein the X domain has an amino acid sequence that shares at least 50% sequence identity with X domains in Table 2.
Claim 25 is drawn to the composition of claim 22 wherein the IscB protein shares at least 80% sequence identity with IscB proteins in Tables 2 and 3. This claim encompasses a broad genus of IscB proteins comprising the required structure recited in claim 22 and sharing 80% sequence identity with IscB proteins in Tables 2 and 3.
The teachings of Table 2 are discussed above as applied to claims 23. Table 2 provides only five protein species comprising all of the domains required by the claim. Of these five species, one species lacks an HNH domain, while the remaining four species comprise a RuvC domain and an HNH domain. The specification fails to teach whether deletion of an entire HNH domain is intended to represent the remaining 20% of the structure that can be varied. Further, with respect to the specie lacking an HNH domain (No. 1), the specification fails to teach which residues within the remaining 20% of sequence can be varied while retaining the claimed structure of the IscB protein. Thus, even where an IscB species omits an entire HNH domain, the specification fails to provide guidance as to which portions of the sequence are structurally dispensable.
In addition, the only structural and functional characterization the specification provided for the RuvC and HNH domain is that a single amino acid substitution (E157A and H212A) in each domain abolishes specific nucleolytic activity ([01042]); However, this characterization is identified for AwaIscB protein, which is NOT included in Tables 2 and 3. The specification does not teach whether the same correlation between structure and function is applicable to species in Tables 2 and 3. Further, this teaching demonstrates that the RuvC and HNH domains are highly sensitive to mutations, yet the specification fails to teach which residues outside of the identified positions can be modified while preserving structure and function. Accordingly, the sequences disclosed in Tables 2 and 3 represent only partial structures and are not representative species across the claimed genus.
The state of the art, Kapitonov teaches IscB2 and Cas9 share relatively high sequence similarity in the RuvC and Bridge Helix domains (Fig. 1, 798, right-column, third paragraph), but Kapitonov does not teach the required N-terminal X domain and C-terminal Y domain, supported by the specification that the N-terminal X domain was previously unidentified ([01035]). Thus, the state of the art does not teach which residues of the remaining 20% of structure can be varied while preserving the required structure and function of IscB proteins.
Based on the preponderance of the evidence, including the relevant teachings of the specification, the absence of working examples, and lack of prior art on IscB protein variants and domain structures, one skilled in the art would conclude that Applicant was not in possession of the claimed genus of IscB proteins.
Response to Arguments
Applicant argues that “both reduced-to-practice species, OgeuIscB and AwaIscB, satisfy the domain architecture requirements of revised claim 22” (see remarks pg. 22, para. 3).
Applicant’s argument has been fully considered and is not persuasive. The breadth of the claim encompasses an enormous number of species merely defined by the structure of comprising at least one domain from a first IscB polypeptide and at least one domain from a second IscB polypeptide. While MPEP 2163 acknowledges that in certain situations “one species adequately supports a genus”, it also acknowledges that “[f]or inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus.” In view of the wide variant species encompassed by the genus, the two examples described above are not enough and does not constitute a representative number of species to describe the whole genus.
Applicant argues that “the nucleotide deaminase, reverse transcriptase, and non-LTR retrotransposon genera listed in claims 45, 54, and 60 respectively are mature, well-characterized enzyme classes” (paragraph bridging pg. 22 and 23).
The amendment to claims 45, 54, and 60 to recite an ωRNA molecule in place of CRISPR-associated single molecule obviates rejections of record under 35 USC 112(a). Further, Applicant’s argument has been fully considered and is persuasive. Thus, the rejection of claims 45, 54, and 60 for failing to comply with written description requirements is withdrawn.
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 22-23, 26-27, 29, 45, 54, and 60 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2, and 14-16, 22, and 25-27 of copending Application No. 18/712,779 in view of Kapitonov et al (ISC, a Novel Group of Bacterial and Archaeal DNA Transposons That Encode Cas9 Homologs; Journal of Bacteriology, 2016, 198(5):797-807), Jinek et al (Science, 2012, 337:816-821), and Doudna (US 2014/0068797A1; Published Date: Mar 06, 2014).
Regarding instant claims 22-23, 26-27, and 29, copending claims of ‘779 recites an IscB polypeptide comprising a RuvC domain and a PLMP domain, which is also referred as the N-terminal X domain in the instant claim ([0133]) (claim 1 and 2), which anticipates the instant claimed genus of IscB protein. ‘779 recites the IscB polypeptide comprises an HNH domain (claim 1). Further, ‘779 recites wherein the IscB polypeptide of claim 1 (a genus encompassing the species IscB protein in the instant claim 22) is about 170 to about 600 amino acids (claim 6), meeting claimed limitation of instant claim 29.
However, ‘779 does not recite wherein the IscB polypeptide comprises one or more nuclear localization signals (NLS).
Doudna teaches CRISPR Cas9 polypeptides with a heterologous sequence that provides for subcellular localization (e.g., an NLS) for targeting to the nucleus ([0241]).
Thus, it would have been obvious to one of ordinary skill in the art to modify ‘779 IscB protein to comprise one or more NLS as taught by Doudna because it would have merely amounted to a simple combination of prior art elements according to known methods to yield predictable results. One would have been motivated to have done so for the advantage of targeting the IscB protein to the nucleus for genome editing. One would have had a reasonable expectation of success in doing so because Doudna teaches structurally similar CRISPR-Cas9 proteins comprising the required NLS.
Regarding instant claims 45, 54, and 60, ‘779 teaches an IscB polypeptide, an ωRNA molecule with the two instantly recited functions, and a functional domain selected from the group consisting of a nucleotide deaminase (as recited in instant claim 45), a reverse transcriptase (as recited in instant claim 54), or a non-LTR retrotransposon (as recited in instant claim 60) (claim 22).
However, ‘779 does not recite wherein the IscB polypeptide is catalytically inactive as recited in the instant claims 45, 54, and 60.
Kapitonov denoted the catalytic amino acid residues in RuvC I, RuvC II, and RuvC III subdomains of the RuvC nuclease domain in IscB and Cas9 (Fig. 1), and IscB1 comprises the RuvC-like domain only, without the HNH domain (pg. 799). In addition, Jinek teaches point mutation D10A inactivates catalytic activity of the RuvC nuclease domain of Cas9 (Fig. 2).
Thus, it would have been obvious to one of ordinary skill in the art to modify ‘779 IscB polypeptide to be catalytically inactive because it would have merely amounted to a simple substitution of prior art elements according to known methods to yield predictable results. One would have been motivated to have done so for the advantage of expanding genome editing applications using catalytically inactive nuclease domains that preserve specific target binding while prevent cleavage. One would have had a reasonable expectation of success in doing so because Kapitonov teaches conserved catalytic residues in both Cas9 and IscB and Jinek teaches successful catalytically inactive Cas9 variants.
This is a provisional nonstatutory double patenting rejection.
Claims 22 and 45 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 5 of copending Application No. 19/271,555 (reference application) in view of Kapitonov et al (Journal of Bacteriology, 2016, 198(5):797-807), Jinek et al (Science, 2012, 337:816-821) and Doudna (US 2014/0068797A1; Published Date: Mar 06, 2014).
Regarding instant claims 22 and 45, ‘555 recites a composition comprising an IscB nickase, one or more ωRNA (i.e., CRISPR-associated single guide molecule) capable of forming a complex with the IscB nickase and directing sequence-specific binding of the complex to one or more targeted nick sites (i.e., the target sequence within the target polynucleotide) (claim 5). The IscB nickase of ‘555 is encompassed within the genus of IscB protein of instant claim 22. All instant limitations are addressed because they are either recited in copending claims are render obvious by prior art in view of Kapitonov, Jinek and Doudna to make the same modification based on the obviousness rationale as discussed above as applied to copending claims of Application No. 18/712,779.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 22 and 60 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 8 of copending Application No. 19/333,523 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding instant claims 22 and 60, ‘523 claim 8 recites a composition of claim 1 which comprises a) programmable DNA-binding protein, b) a non-long terminal repear (non-LTR) retrotransposon capable of associating with the programmable DNA-binding protein, and c) a donor construct comprising a donor polynucleotide for insertion into the target polynucleotide and an engineered binding element capable of forming a complex with the non-LTR retrotransposon polypeptide. ‘523 further recites wherein the DNA-binding protein is an OMEGA protein that is an IscB protein, and one or more ωRNA (i.e., CRISPR-associated single guide molecule) capable of forming a complex with the IscB protein and directing sequence-specific binding of the complex to the target sequence within the target polynucleotide (claim 8). Accordingly, claim 8 of ‘523 recites the composition of the instant claim 60. The IscB protein of ‘555 is encompassed within the genus of IscB protein of instant claim 22. All instant limitations are addressed because they are either recited in copending claims are render obvious by prior art in view of Kapitonov, Jinek and Doudna to make the same modification based on the obviousness rationale as discussed above as applied to copending claims of Application No. 18/712,779.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 22 and 60 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 2 of copending Application No. 18/276,471 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding instant claims 22 and 60, ‘471 claim 2 teaches a composition of claim 1 which comprises a) first site-specific nuclease, b) a non-LTR) retrotransposon polypeptide capable of forming a complex with the first site-specific nuclease, and c) a donor construct comprising a donor polynucleotide for insertion into the target polynucleotide and comprising one or more elements capable of forming a complex with the non-LTR retrotransposon polypeptide. ‘471 further teaches wherein the first site-specific nuclease is an IscB polypeptide, and the composition further comprises a nucleic acid component capable of forming a complex with the IscB polypeptide and directing binding of the complex to the target sequence (claim 2). Accordingly, claim 2 of ‘471 teaches the composition of the instant claim 60. The IscB polypeptide of ‘471 is encompassed within the genus of IscB protein of instant claim 22. All instant limitations are addressed because they are either recited in copending claims are render obvious by prior art in view of Kapitonov, Jinek and Doudna to make the same modification based on the obviousness rationale as discussed above as applied to copending claims of Application No. 18/712,779.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1, 6-8, 12, 16-17, and 33 are allowable.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/QIWEN SU-TOBON/
Examiner
Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636
Prosecution Insights