Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This application 18/067,214 filed on 12/16/2022 claims priority of provisional application 63/265,661 filed on 12/17/2021.
Restriction/Election
Applicant’s election without traverse of Group I invention, claims 87-91, 95, 99-106, 109-111, 114-122, in the reply filed on 9/15/2025 is acknowledged.
Regarding Species election (I) of integration enzyme, Applicants elected Bxb1 [recited in claim 111] in the reply filed on 9/15/2025.
Regarding Species election (II), (III), and (IV) regarding SEQ ID NOs of integration enzyme, attB, and attP, Applicants elected an integration enzyme comprising at least 90% to an amino acid sequence of SEQ ID NO: 11 [recited in claim 114] for species election (II); an attB nucleic acid sequence having SEQ ID NO:37 [recited in claim 120] for species election (III); and an attP nucleic acid sequence having SEQ ID NO:38 [recited in claim 121] for species election (III), in the reply filed on 2/3/2026, which is in response to Notice of Non-Compliant Amendments mailed on 01/15/2026.
Claims 1-86, 92-94, 96-98, 107-108, 112-113, 123-133, and 135-169 are cancelled. It is noted claim 120 is marked as both “(Cancelled)” and “(Previously presented)” in the claim set field on 09/15/2026, and is interpretated as “(Previously presented)”.
Claims 87-91, 95, 99-106, 109-111, 114-122, and 134 are pending.
Claim 134 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 9/15/2025.
Claims 87-91, 95, 99-106, 109-111, and 114-122 are currently under examination to the extent of elected species: Bxb1 [recited in claim 111]; SEQ ID NO: 11 [recited in claim 114 and limitation k) of claim 122]; SEQ ID NO: 37 [recited in claim 120 and limitation k) of claim 122]; and SEQ ID NO: 38 [recited in claim 121 and limitation k) of claim 122].
SEQ ID NO: 11 moltype = AA length 500
FEATURE Location/Qualifiers
REGION 1.. 500
note= Mycobacterium phage Bxbl
source 1.. 500
mol type pro tein
organism synthetic construct
SEQUENCE, 11
MRALVVIRLS RVTDATTSPE RQLESCQQLC AQRGWDVVGV AEDLDVSGAV DPFDRKRRPN 60
LARWLAFEEQ PFDVIVAYRV DRLTRSIRHL QQLVHWAEDH KKLVVSATEA HFDTTTPFAA 120
VVIALMGTVA QMELEAIKER NRSAAHFNIR AGKYRGSLPP WGYLPTRVDG EWRLVPDPVQ 180
RERILEVYHR VVDNHEPLHL VAHDLNRRGV LSPKDYFAQL QGREPQGREW SATALKRSMI 240
SEAMLGYATL NGKTVRDDDG APLVRAEPIL TREQLEALRA ELVKTSRAKP AVSTPSLLLR 300
VLFCAVCGEP AYKFAGGGRK HPRYRCRSMG FPKHCGNGTV AMAEWDAFCE EQVLDLLGDA 360
ERLEKVWVAG SDSAVELAEV NAELVDLTSL IGSPAYRAGS PQREALDARI AALAARQEEL 420
EGLEARPSGW EWRETGQRFG DWWREQDTAA KNTWLRSMNV RLTFDVRGGL TRTIDFGDLQ 480
EYEQHLRLGS VVERLHTGMS 500
SEQ ID NO: 37 moltype = DNA length= 46
FEATURE Location/Qualifiers
misc feature 1. .46
note= attB site sequence
source 1. .46
mol_type = other DNA
organism = synthetic construct
SEQUENCE: 37
ggccggcttg tcgacgacgg cggtctccgt cgtcaggatc atccgg 46
SEQ ID NO: 38 moltype = DNA length= 52
FEATURE Location/Qualifiers
misc feature 1. .52
note= attB site sequence
source 1. .52
mol_type = other DNA
organism = synthetic construct
SEQUENCE: 38
gtggtttgtc tggtcaacca ccgcggtctc agtggtgtac ggtacaaacc ca
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 109 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 109 filed on 09/15/2025 reads as follows: The complex of claim 106, comprising any one or more of the linker sequences recited in Table 4.
Table 4 disclosed in the Specification filed on 12/16/2022, pages 44-45, is copied below.
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MPEP 2173.05(s) Reference to Figures or Tables [R-10.2019]
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)
Reference characters corresponding to elements recited in the detailed description and the drawings may be used in conjunction with the recitation of the same element or group of elements in the claims. Generally, the presence or absence of such reference characters does not affect the scope of a claim. See MPEP § 608.01(m) for information pertaining to the treatment of reference characters in a claim.
In instant case, claim 109 can be complete in itself by recitation of SEQ ID numbers of the linker sequences.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 87-89, 91, 95, 99-106, 109-111, and 115-117 are rejected under 35 U.S.C. 102(a)(1) and 102 (a)(2) as being anticipated by (i) Liu et al. (2020) (WO 2020/191245 A1, PCT/US2020/023727, international publication date 09/24/2020, international filing date 03/19/2020), and alternatively (ii) Liu et al. (2020) (WO 2020/191241 A1, PCT/US2020/023723, international publication date 09/24/2020, international filing date 03/19/2020, cited as Foreign document number 4 in the IDS filed by Applicants on 11/28/2023)
It is noted that the disclosures of WO 2020/191245 A1 and WO 2020/191241 A1 are significantly duplicative to the extent of being verbatim, and the annotation in terms of Figure and paragraph numbers indicated in the rejection documented below is based on the disclosure of WO 2020/191245 A1.
Regarding claim 87, Liu et al. (2020) teaches that “The present disclosure provides compositions and methods for conducting prime editing of a target DNA molecule (e.g., a genome) that enables the incorporation of a nucleotide change and/or targeted mutagenesis. The nucleotide change can include a single-nucleotide change (e.g., any transition or any transversion), an insertion of one or more nucleotides, or a deletion of one or more nucleotides. More in particular, the disclosure provides fusion proteins comprising nucleic acid programmable DNA binding proteins (napDNAbp) and a polymerase (e.g., reverse transcriptase), which is guided to a specific DNA sequence by a modified guide RNA, named an PEgRNA. The PEgRNA has been altered (relative to a standard guide RNA) to comprise an extended portion that provides a DNA synthesis template sequence which encodes a single strand DNA flap, which is homologous to a strand of the targeted endogenous DNA sequence to be edited, but which contains the desired one or more nucleotide changes and which, following synthesis” (See Abstract and Fig. 1A).
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Regarding claims 88 and 89, Liu et al. (2020) teaches that “FIG. 3D provides the structure of an exemplary PEgRNA contemplated herein.”
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FIG. 3D provides the structure of an exemplary PEgRNA contemplated herein. The
PEgRNA comprises three main component elements ordered in the 5' to 3' direction, namely:
a spacer, a gRNA core, and an extension arm at the 3' end. The extension arm may further be
divided into the following structural elements in the 5' to 3' direction, namely: a primer
binding site (A), an edit template (B), and a homology arm (C). In addition, the PEgRNA
may comprise an optional 3' end modifier region (el) and an optional 5' end modifier region
(e2). Still further, the PEgRNA may comprise a transcriptional termination signal at the 3'
end of the PEgRNA (not depicted). These structural elements are further defined herein. The
depiction of the structure of the PEgRNA is not meant to be limiting and embraces variations
in the arrangement of the elements. For example, the optional sequence modifiers (el) and
(e2) could be positioned within or between any of the other regions shown, and not limited to
being located at the 3' and 5' ends. The PEgRNA could comprise, in certain embodiments,
secondary RNA structure, such as, but not limited to, hairpins, stem/loops, toe loops, RNA binding protein recruitment domains (e.g., the MS2 aptamer which recruits and binds to the
MS2cp protein). For instance, such secondary structures could be position within the spacer,
the gRNA core, or the extension arm, and in particular, within the el and/or e2 modifier
regions. In addition to secondary RNA structures, the PEgRNAs could comprise (e.g.,
within the el and/or e2 modifier regions) a chemical linker or a poly(N) linker or tail, where
"N" can be any nucleobase. In some embodiments (e.g., as shown in FIG. 72(c)), the
chemical linker may function to prevent reverse transcription of the sgRNA scaffold or core.
In addition, in certain embodiments (e.g., see FIG. 72(c)), the extension arm (3) could be
comprised of RNA or DNA, and/or could include one or more nucleobase analogs (e.g.,
which might add functionality, such as temperature resilience). Still further, the orientation
of the extension arm (3) can be in the natural 5 '-to-3' direction, or synthesized in the opposite
orientation in the 3'-to-5' direction (relative to the orientation of the PEgRNA molecule
overall). It is also noted that one of ordinary skill in the art will be able to select an
appropriate DNA polymerase, depending on the nature of the nucleic acid materials of the
extension arm (i.e., DNA or RNA), for use in prime editing that may be implemented either
as a fusion with the napDNAbp or as provided in trans as a separate moiety to synthesize the
desired template-encoded 3' single-strand DNA flap that includes the desired edit. For
example, if the extension arm is RNA, then the DNA polymerase could be a reverse
transcriptase or any other suitable RNA-dependent DNA polymerase. However, if the
extension arm is DNA, then the DNA polymerase could be a DNA-dependent DNA
polymerase. In various embodiments, provision of the DNA polymerase could be in trans,
e.g., through the use of an RNA-protein recruitment domain (e.g., an MS2 hairpin installed
on the PEgRNA (e.g., in the el or e2 region, or elsewhere and an MS2cp protein fused to the
DNA polymerase, thereby co-localizing the DNA polymerase to the PEgRNA). It is also
noted that the primer binding site does not generally form a part of the template that is used
by the DNA polymerase (e.g., reverse transcriptase) to encode the resulting 3' single-strand
DNA flap that includes the desired edit. Thus, the designation of the "DNA synthesis
template" refers to the region or portion of the extension arm (3) that is used as a template by
the DNA polymerase to encode the desired 3' single-strand DNA flap containing the edit and
regions of homology to the 5' endogenous single strand DNA flap that is replaced by the 3'
single strand DNA strand product of prime editing DNA synthesis. In some embodiments,
the DNA synthesis template includes the "edit template" and the "homology arm", or one or
more homology arms, e.g., before and after the edit template. The edit template can be as
small as a single nucleotide substitution, or it may be an insertion, or an inversion of DNA.
In addition, the edit template may also include a deletion, which can be engineered by
encoding homology arm that contains a desired deletion. In other embodiments, the DNA
synthesis template may also include the e2 region or a portion thereof. For instance, if the e2
region comprises a secondary structure that causes termination of DNA polymerase activity,
then it is possible that DNA polymerase function will be terminated before any portion of the
e2 region is actual encoded into DNA. It is also possible that some or even all of the e2
region will be encoded into DNA. How much of e2 is actually used as a template will
depend on its constitution and whether that constitution interrupts DNA polymerase function.
Regarding claim 91, Liu et al. (2020) teaches that “FIG. 3F depicts the interaction of a typical PEgRNA with a target site of a double stranded DNA and the concomitant production of a 3' single stranded DNA flap containing the genetic change of interest. The double strand DNA is shown with the top strand (i.e., the target strand) in the 3' to 5' orientation and the lower strand (i.e., the PAM strand or non-target strand) in the 5' to 3' direction”.
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FIG. 3F depicts the interaction of a typical PEgRNA with a target site of a double stranded DNA and the concomitant production of a 3' single stranded DNA flap containing the genetic change of interest. The double strand DNA is shown with the top strand (i.e., the target strand) in the 3' to 5' orientation and the lower strand (i.e., the PAM strand or non-target strand) in the 5' to 3' direction. The top strand comprises the complement of the "protospacer" and the complement of the PAM sequence and is referred to as the "target strand" because it is the strand that is target by and anneals to the spacer of the PEgRNA. The complementary lower strand is referred to as the "non-target strand" or the "PAM strand" or the "protospacer strand" since it contains the PAM sequence (e.g., NGG) and the protospacer. Although not shown, the PEgRNA depicted would be complexed with a Cas9 or equivalent domain of a prime editor fusion protein. As shown in the schematic, the spacer of the PEgRNA anneals to the complementary region of the protospacer on the target strand. This interaction forms as DNA/RNA hybrid between the spacer RNA and the complement of the protospacer DNA, and induces the formation of an R loop in the protospacer. As taught elsewhere herein, the Cas9 protein (not shown) then induces a nick in the non-target strand, as shown. This then leads to the formation of the 3' ssDNA flap region immediately upstream of the nick site which, in accordance with *z*, interacts with the 3' end of the PEgRNA at the primer binding site. The 3' end of the ssDNA flap (i.e., the reverse
transcriptase primer sequence) anneals to the primer binding site (A) on the PEgRNA,
thereby priming reverse transcriptase. Next, reverse transcriptase (e.g., provided in trans or
provided cis as a fusion protein, attached to the Cas9 construct) then polymerizes a single
strand of DNA which is coded for by the DNA synthesis template (including the edit
template (B) and homology arm (C)). The polymerization continues towards the 5' end of the
extension arm. The polymerized strand of ssDNA forms a ssDNA 3' end flap which, as
describe elsewhere (e.g., as shown in FIG. lG), invades the endogenous DNA, displacing the
corresponding endogenous strand (which is removed as a 5' ended DNA flap of endogenous
DNA), and installing the desired nucleotide edit (single nucleotide base pair change, deletions, insertions (including whole genes) through naturally occurring DNA repair/replication rounds. (See [0084]).
Regarding claims 95, and 99-101, Liu et al. (2020) teaches “FIG. 1A provides a schematic of an exemplary process for introducing a single nucleotide change, and/or insertion, and/or deletion into a DNA molecule (e.g., a genome) using a fusion protein comprising a reverse transcriptase fused to a Cas9 protein in complex with an extended guide RNA molecule”.
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FIG. 1A provides a schematic of an exemplary process for introducing a single
nucleotide change, and/or insertion, and/or deletion into a DNA molecule (e.g., a genome)
using a fusion protein comprising a reverse transcriptase fused to a Cas9 protein in complex
with an extended guide RNA molecule. In this embodiment, the guide RNA is extended at
the 3' end to include a reverse transcriptase template sequence. The schematic shows how a
reverse transcriptase (RT) fused to a Cas9 nickase, in a complex with a guide RNA (gRNA),
binds the DNA target site and nicks the PAM-containing DNA strand adjacent to the target
nucleotide. The RT enzyme uses the nicked DNA as a primer for DNA synthesis from the
gRNA, which is used as a template for the synthesis of a new DNA strand that encodes the desired edit. The editing process shown may be referred to as target-primed reverse
transcription editing (TRT editing) or equivalently, "prime editing" (See [0069]).
Regarding claim 102, Liu et al. (2020) teaches that “In certain embodiments, the napDNAbp has a nickase activity. The napDNAbp may also be a Cas9 protein or functional equivalent thereof, such as a nuclease active Cas9, a nuclease inactive Cas9 (dCas9), or a Cas9 nickase (nCas9). In certain embodiments, the napDNAbp is selected from the group consisting of: Cas9, Cas12e, Casl2d, Cas12a, Casl2bl, Cas13a, Cas12c, and Argonaute and optionally has
a nickase activity” (See [0013] and [0014]). Liu et al. (2020) further teaches that “An exemplary fusion protein is depicted in FIG. 14, which shows a fusion protein comprising an ML V reverse transcriptase ("ML V-RT") fused to a nickase Cas9 ("Cas9(H840A)") via a linker sequence. This example is not intended to limit scope of fusion proteins that may be utilized for the prime editor (PE) system described herein. (See [0525])
Regarding claim 103, Liu et al. (2020) teaches that “Exemplary enzymes for use with the herein disclosed prime editors can include, but are not limited to, M-MLV reverse transcriptase and RSV reverse transcriptase. Enzymes having reverse transcriptase activity are commercially available. In certain embodiments, the reverse transcriptase provided in trans to the other components of the prime editor (PE) system. That is, the reverse transcriptase is expressed or otherwise provided as an individual component, i.e., not as a fusion protein with a napDNAbp. A person of ordinary skill in the art will recognize that wild type reverse transcriptases, including but not limited to, Moloney Murine Leukemia Virus (M-MLV); Human Immunodeficiency Virus (HIV) reverse transcriptase and avian Sarcoma-Leukosis Virus (ASL V) reverse transcriptase, which includes but is not limited to Rous Sarcoma Virus (RSV) reverse transcriptase, Avian Myeloblastosis Virus (AMV) reverse transcriptase, Avian Erythroblastosis Virus (AEV) Helper Virus MCA V reverse transcriptase, Avian Myelocytomatosis Virus MC29 Helper Virus MCAV reverse transcriptase, Avian Reticuloendotheliosis Virus (REV-T) Helper Virus REV-A reverse transcriptase, Avian Sarcoma Virus UR2 Helper Virus UR2AV reverse transcriptase, Avian Sarcoma Virus Y73 Helper Virus YA V reverse transcriptase, Rous Associated Virus (RAV) reverse transcriptase, and Myeloblastosis Associated Virus (MAV) reverse transcriptase may be suitably used in the subject methods and composition described herein (See [0433] and [0434]).
Regarding claim 104, Liu et al. (2020) teaches that “In various embodiments, the reverse transcriptase may be a variant reverse transcriptase. As used herein, a "variant reverse transcriptase" includes any naturally occurring or genetically engineered variant comprising one or more mutations (including singular mutations, inversions, deletions, insertions, and rearrangements) relative to a reference sequences (e.g., a reference wild type sequence). RT naturally have several activities, including an RNA-dependent DNA polymerase activity, ribonuclease H activity, and DNA-dependent DNA polymerase activity. Collectively, these activities enable the enzyme to convert single-stranded RNA into double-stranded cDNA. In retroviruses and retrotransposons, this cDNA can then integrate into the host genome, from which new RNA copies can be made via host-cell transcription. Variant RT's may comprise a mutation which impacts one or more of these activities (either which reduces or increases these activities, or which eliminates these activities all together). In addition, variant RTs may comprise one or more mutations which render the RT more or less stable, less prone to aggregation, and facilitates purification and/or detection, and/or other the modification of properties or characteristics” (See [0437]).
Regarding claim 105, Liu et al. (2020) teaches that “For example, the prime editors disclosed herein may include a truncated version of MML-V reverse transcriptase. In this embodiment, the reverse transcriptase contains 4 mutations (D200N, T306K, W313F, T330P; noting that the L603W mutation present in PE2 is no longer present due to the truncation). The DNA sequence encoding this truncated editor is 522 bp smaller than PE2, and therefore makes its potentially useful for applications where delivery of the DNA sequence is challenging due to its size (i.e., adeno-associated virus and lentivirus delivery” (See [0457]).
Regarding claim 106, Liu et al. (2020) teaches that “In various embodiments, the fusion proteins may comprise any suitable structural configuration. For example, the fusion protein may comprise from the N-terminus to the C-terminus direction, a napDNAbp fused to a polymerase (e.g., DNA-dependent DNA polymerase or RNA-dependent DNA polymerase, such as, reverse transcriptase). In other embodiments, the fusion protein may comprise from the N-terminus to the C-terminus direction, a polymerase (e.g., a reverse transcriptase) fused to a napDNAbp. The fused domain may optionally be joined by a linker, e.g., an amino acid sequence. In other embodiments, the fusion proteins may comprise the structure NH2-[napDNAbp]-[polymerase]-COOH; or NH2-[polymerase]-[napDNAbp]-COOH, wherein each instance of "]-[" indicates the presence of an optional linker sequence. In embodiments wherein the polymerase is a reverse transcriptase, the fusion proteins may comprise the structure NH2-[napDNAbp ]-[RT]-COOH; or NH2-[RT]-[napDNAbp]-COOH, wherein each instance of"][" indicates the presence of an optional linker sequence (See [0524]).
Regarding claim 109, Liu et al. (2020) teaches that” Protein linkers encoded as nucleotides inserted between the target gene sequence and the inserted immunogenicity epitope nucleotide sequence may need to be engineered as part of this invention to facilitate immune system recognition, cellular trafficking, protein function, or protein folding of the targeted gene. These inserted nucleotide-encoded protein linkers may include (but are not limited to) variable lengths and sequences of the XTEN linker or variable lengths and sequences of Glycine-Serine linkers. These engineered linkers have been previous used to successfully facilitate protein fusions. Examplary linkers may include any of those described herein, including the amino acid sequence (GGGGS)n (SEQ ID NO: 165), (G)n (SEQ ID NO: 166), (EAAAK)n (SEQ ID NO: 167), (GGS)n (SEQ ID NO: 168), (SGGS)n (SEQ ID NO: 169), (XP)n (SEQ ID NO: 170), or any combination thereof, wherein n is independently an integer between 1 and 30, and wherein Xis any amino acid. In some embodiments, the linker comprises the amino acid sequence (GGS)n (SEQ ID NO: 176), wherein n is 1, 3, or 7. In some embodiments, the linker comprises the amino acid sequence SGSETPGTSESATPES (SEQ ID NO: 171). In some embodiments, the linker comprises the amino acid sequence SGGSSGGSSGSETPGTSESATPESSGGSSGGS (SEQ ID NO: 172). In some embodiments, the linker comprises the amino acid sequence
SGGSGGSGGS (SEQ ID NO: 173). In some embodiments, the linker comprises the amino acid sequence SGGS (SEQ ID NO: 174)” (See [0812]).
Regarding claims 110, 111, and 115-117, Liu et al. (2020) teaches that “Table 8. Large serine integrases and SSR (site-specific recombinase) target sequences”
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Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 87, 88, and 90 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (2020) (WO 2020/191245 A1, international publication date 09/24/2020, international filing date 03/19/2020), alternatively over Liu et al. (2020) (WO 2020/191241 A1, PCT/US2020/023723, international publication date 09/24/2020, international filing date 03/19/2020, cited as Foreign document number 4 in the IDS filed by Applicants on 11/28/2023),
in view of Brinker et al. (2015) (US 2015/0010475 A1, US application number 14/369,741, publication date 01/08/2015)
The teachings of Liu et al. (2020) (WO 2020/191245 A1), alternatively Liu et al. (2020) (WO 2020/191241 A1), have been documented above in the rejection of Claims 87-89, 91, 95, 99-106, 109-111, and 115-117 under 35 U.S.C. 102(a)(1) and 102 (a)(2).
Liu et al. (2020) does not explicitly teach SEQ ID NO: 54 recited in claim 90. Claim 90 depends from claim 88, which depends from claim 87.
Brinker et al. (2015) teaches that “The efficacy and rate of cap side assembly are maximized in the presence of the MS2 translational operator, a 19-nucleotide RNA stem-loop (SEQ ID NO:32, SEQ ID NO:33), that via its interaction with coat protein, mediates exclusive encapsidation of the MS2 genome during bacteriophage replication. See, Wu, et al., Bioconjugate Chemistry, 6(5):587-595 (1995); Pickett & Peabody, NuclAcids. Res., 21 (19):4621-4626 (1993) and Uhlenback, Nature Structure Biology, 5(3): 174-174 (1998). The MS2 operator, orpac site, can promote efficient encapsidation of non-genomic materials, such as the polypeptide toxins, including the A-chain of ricin toxin, among others, within the interior volume ofMS2 VLPs upon conjugation of the pac site to the cargo of interest. MS2 VLPs will also encapsidate RNA hairpins with sequences that differ from that of the native operator, as well as heterologous nucleic acids, including singe- and double-stranded RNA and DNA less than 3 bkp in length. Accordingly, the sequence of the pac site can be modified as long as the modification does not prevent the RNA molecule from inducing VLP self assembly. For example, the pac site can further comprise a spacer molecule, such as a polyU nucleotide (e.g. (U)3_9))” (See [0234]).
The alignment of SEQ ID NO: 54 of instant application to SEQ ID NO: 33 of Brinker et al. (2015) (US 2015/0010475 A1) is provided below.
Title: US-18-067-214-54
Perfect score: 19
Sequence: 1 acatgaggatcacccatgt 19
Scoring table: IDENTITY_NUC
Gapop 10.0 , Gapext 1.0
Searched: 206607289 unique seqs, 25283810505 residues
Total number of hits satisfying chosen parameters: 413214578
Minimum DB seq length: 1
Maximum DB seq length: 40000
Post-processing: Minimum Match 0%
Maximum Match 100%
Listing first 45 summaries
Database : Pending_Patents_NA_Main:*
RESULT 1
US-14-369-741B-33
(NOTE: this sequence has 180 duplicates in the database searched.
See complete list at the end of this report)
Sequence 33, US/14369741B
GENERAL INFORMATION
APPLICANT: STC.UNM
APPLICANT: BRINKER, C. Jeffrey
APPLICANT: PEABODY, David S
APPLICANT: WHARTON, Walker
APPLICANT: CHACKERIAN, Bryce
APPLICANT: ASHLEY, Carlee Erin
APPLICANT: WILLMAN, Cheryl L.
APPLICANT: CARNES, Eric c.
APPLICANT: EPLER, Katherine
APPLICANT: CASTILLO, Robert Eric
TITLE OF INVENTION: CRLF-2 BINDING PEPTIDES, PROTOCELLS AND VIRAL-LIKE PARTICLES
TITLE OF INVENTION: USEFUL IN THE TREATMENT OF CANCER, INCLUDING ACUTE LYMPHOBLASTIC
TITLE OF INVENTION: LEUKEMIA (ALL)
FILE REFERENCE: N12-185US_Nat
CURRENT APPLICATION NUMBER: US/14/369,741B
CURRENT FILING DATE: 2014-06-30
PRIOR APPLICATION NUMBER: PCT/US12/72297
PRIOR FILING DATE: 2012-12-31
PRIOR APPLICATION NUMBER: 61/581,915
PRIOR FILING DATE: 2011-12-30
NUMBER OF SEQ ID NOS: 35
SEQ ID NO 33
LENGTH: 19
TYPE: DNA
ORGANISM: Artificial
FEATURE:
OTHER INFORMATION: RNA stem-loop
Query Match 100.0%; Score 19; Length 19;
Best Local Similarity 100.0%;
Matches 19; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ACATGAGGATCACCCATGT 19
|||||||||||||||||||
Db 1 ACATGAGGATCACCCATGT 19
It would have been prima facie obvious for a skilled artisan to incorporate the disclosure of “MS2 translational operator, a 19-nucleotide RNA stem-loop (SEQ ID NO: 32, SEQ ID NO: 33)” taught by Brinker et al. (2015) into the teachings in FIG. 3D providing the structure of an exemplary PEgRNA of Liu et al. (2020) (WO 2020/191245 A1, PCT/US2020/023727) regarding “The PEgRNA could comprise, in certain embodiments, secondary RNA structure, such as, but not limited to, hairpins, stem/loops, toe loops, RNA binding protein recruitment domains (e.g., the MS2 aptamer which recruits and binds to the MS2cp protein)” to arrive at instant claim 90 with reasonable expectation of success because Liu et al. (2020) teaches molecular function of RNA structure of the MS2 stem/loops whereas Brinker et al. (2015) teaches the MS 2 sequences being a 19-nucleotide RNA stem-loop (SEQ ID NO:32, SEQ ID NO:33)”.
A skilled artisan would be motivated to combine the teachings Brinker et al. (2015) with the teachings of Liu et al. (2020) et al. because (i) Liu et al. (2020) et al. that the PEgRNA could comprise, in certain embodiments, secondary RNA structure, such as, but not limited to, hairpins, stem/loops, toe loops, RNA binding protein recruitment domains (e.g., the MS2 aptamer which recruits and binds to the MS2cp protein) in FIG. 3D, (ii) Brinker et al. (2015) teaches the MS 2 sequences being a 19-nucleotide RNA stem-loop (SEQ ID NO: 32, SEQ ID NO:33)” (See [0234]).
Claims 87, 110, 114-116, 118-122 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (2020) (WO 2020/191245 A1, international publication date 09/24/2020, international filing date 03/19/2020), alternatively over Liu et al. (2020) (WO 2020/191241 A1, PCT/US2020/023723, international publication date 09/24/2020, international filing date 03/19/2020, cited as Foreign document number 4 in the IDS filed by Applicants on 11/28/2023), in view of Padidam (2006) (US 2006/0172377 A1, US application number 11/049,552, publication date 08/03/2006).
Then teachings of Liu et al. (2020) (WO 2020/191245 A1), alternatively Liu et al. (2020) (WO 2020/191241 A1), have been documented above in the rejection of Claims 87-91, 95, 99-106, 109-111, and 115-117 under 35 U.S.C. 102(a)(1) and 102 (a)(2).
Liu et al. (2020) does not explicitly teach SEQ ID NO: 11 recited in claim 114; the length variations of attB and/or attP recited in claims 118-119; SEQ ID NO: 37 recited in claim 120, and SEQ ID NO: 38 recited in claim 121.
Claim 114 depends from claim 110, which depends from claim 87. Claims 120 and 121 depend from claim 116, which depend from claims 115, 110 and 87.
Padidam (2006) teaches that “The present invention provides a method for obtaining
site-specific recombination in a eukaryotic cell, the method comprising providing a eukaryotic cell that comprises a first recombination attachment site and a second recombination attachment site; contacting the first and second recombination attachment sites with a prokaryotic recombinase polypeptide, resulting in recombination between the recombination attachment sites, wherein the recombinase polypeptide can mediate recombination between the first and second recombination attachment sites, the first recombination attachment site is a phage genomic recombination attachment site (attP) or a bacterial genomic recombination attachment
site (attB), the second recombination site is attB or attP, and the recombinase is selected from the group consisting of a Listeria monocytogenes phage recombinase, a Streptococcus pyogenes phage recombinase, a Bacillus subtilis phage recombinase, a Mycobacterium tuberculosis phage recombinase and a Mycobacterium smegmatis phage recombinase, provided that when the first recombination attachment site is attB, the second recombination attachment site is attP and
when the first recombination attachment site is attP, the second recombination attachment site is attB. The invention also describes compositions, vectors, and methods of use thereof, for the generation of transgenic cells, tissues, plants, and animals. The compositions, vectors and methods of the present invention are also useful in gene therapy applications” (See Title and Abstract).
Padidam (2006) further teaches that “The present invention also relates to a vector for site-specific integration of a polynucleotide sequence into the genome of an isolated eukaryotic cell, said vector comprising a polynucleotide of interest, and a second recombination attB or attP site, wherein said second recombination attB or attP site comprises a polynucleotide sequence that recombines with a first recombination attP or attB site or pseudo attP or pseudo attB site in the genome of said isolated eukaryotic cell and said recombination occurs in the presence of a site-specific recombinase selected from the group consisting of a Listeria monocytogenes phage
recombinase, a Streptococcus pyogenes phage recombinase, a Bacillus subtilis phage recombinase, a Mycobacterium tuberculosis phage recombinase and a Mycobacterium smegmatis phage recombinase, provided that when the first recombination site is attB or pseudo attB, the second recombination site is attP and when the first recombination site is attP or pseudo attP, the second recombination site is attB. Preferably the recombinase is selected from the group consisting of anA118 recombinase, a SF370.l recombinase, a SPbc2 recombinase, a fRv1 recombinase, and a Bxb1 recombinase” (See [0126]).
The alignment of SEQ ID NO: 11 of instant application to SEQ ID NO: 6 of Padidam (2006) (US 2006/0172377 A1, US application number 11/049,552, publication date 08/03/2006). is provided below.
Title: US-18-067-214-11
Perfect score: 2613
Sequence: 1 MRALVVIRLSRVTDATTSPE..........EYEQHLRLGSVVERLHTGMS 500
Scoring table: BLOSUM62
Gapop 10.0 , Gapext 0.5
Searched: 17250840 unique seqs, 1939488216 residues
Total number of hits satisfying chosen parameters: 17250840
Minimum DB seq length: 1
Maximum DB seq length: 40000
Post-processing: Minimum Match 0%
Maximum Match 100%
Listing first 45 summaries
RESULT 1
US-11-049-552A-6
(NOTE: this sequence has 37 duplicates in the database searched.
See complete list at the end of this report)
Sequence 6, US/11049552A
Publication No. US20060172377A1
GENERAL INFORMATION
APPLICANT: Padidam, Malla
TITLE OF INVENTION: Site-Specific Serine Recombinases and Methods of Their Use
FILE REFERENCE: A01505-US
CURRENT APPLICATION NUMBER: US/11/049,552A
CURRENT FILING DATE: 2005-02-02
NUMBER OF SEQ ID NOS: 21
SEQ ID NO 6
LENGTH: 500
TYPE: PRT
ORGANISM: Putative recombinase of mycobacteriophage Bxb1
Query Match 100.0%; Score 2613; Length 500;
Best Local Similarity 100.0%;
Matches 500; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MRALVVIRLSRVTDATTSPERQLESCQQLCAQRGWDVVGVAEDLDVSGAVDPFDRKRRPN 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MRALVVIRLSRVTDATTSPERQLESCQQLCAQRGWDVVGVAEDLDVSGAVDPFDRKRRPN 60
Qy 61 LARWLAFEEQPFDVIVAYRVDRLTRSIRHLQQLVHWAEDHKKLVVSATEAHFDTTTPFAA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 LARWLAFEEQPFDVIVAYRVDRLTRSIRHLQQLVHWAEDHKKLVVSATEAHFDTTTPFAA 120
Qy 121 VVIALMGTVAQMELEAIKERNRSAAHFNIRAGKYRGSLPPWGYLPTRVDGEWRLVPDPVQ 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VVIALMGTVAQMELEAIKERNRSAAHFNIRAGKYRGSLPPWGYLPTRVDGEWRLVPDPVQ 180
Qy 181 RERILEVYHRVVDNHEPLHLVAHDLNRRGVLSPKDYFAQLQGREPQGREWSATALKRSMI 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 RERILEVYHRVVDNHEPLHLVAHDLNRRGVLSPKDYFAQLQGREPQGREWSATALKRSMI 240
Qy 241 SEAMLGYATLNGKTVRDDDGAPLVRAEPILTREQLEALRAELVKTSRAKPAVSTPSLLLR 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 SEAMLGYATLNGKTVRDDDGAPLVRAEPILTREQLEALRAELVKTSRAKPAVSTPSLLLR 300
Qy 301 VLFCAVCGEPAYKFAGGGRKHPRYRCRSMGFPKHCGNGTVAMAEWDAFCEEQVLDLLGDA 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 VLFCAVCGEPAYKFAGGGRKHPRYRCRSMGFPKHCGNGTVAMAEWDAFCEEQVLDLLGDA 360
Qy 361 ERLEKVWVAGSDSAVELAEVNAELVDLTSLIGSPAYRAGSPQREALDARIAALAARQEEL 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 ERLEKVWVAGSDSAVELAEVNAELVDLTSLIGSPAYRAGSPQREALDARIAALAARQEEL 420
Qy 421 EGLEARPSGWEWRETGQRFGDWWREQDTAAKNTWLRSMNVRLTFDVRGGLTRTIDFGDLQ 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 EGLEARPSGWEWRETGQRFGDWWREQDTAAKNTWLRSMNVRLTFDVRGGLTRTIDFGDLQ 480
Qy 481 EYEQHLRLGSVVERLHTGMS 500
||||||||||||||||||||
Db 481 EYEQHLRLGSVVERLHTGMS 500
SEQ ID NO: 17 of Padidam (2006) (US 2006/0172377 A1)
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190
706
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The alignment of SEQ ID NO: 37 of instant application to SEQ ID NO: 17 of Padidam (2006) (US 2006/0172377 A1, US application number 11/049,552, publication date 08/03/2006) is provided below.
Title: US-18-067-214-37
Perfect score: 46
Sequence: 1 ggccggcttgtcgacgacgg..........ccgtcgtcaggatcatccgg 46
Scoring table: IDENTITY_NUC
Gapop 10.0 , Gapext 1.0
Searched: 71052184 unique seqs, 17172728613 residues
Total number of hits satisfying chosen parameters: 142104368
Minimum DB seq length: 1
Maximum DB seq length: 40000
Post-processing: Minimum Match 0%
Maximum Match 100%
RESULT 2
US-11-049-552A-17
(NOTE: this sequence has 28 duplicates in the database searched.
See complete list at the end of this report)
Sequence 17, US/11049552A
Publication No. US20060172377A1
GENERAL INFORMATION
APPLICANT: Padidam, Malla
TITLE OF INVENTION: Site-Specific Serine Recombinases and Methods of Their Use
FILE REFERENCE: A01505-US
CURRENT APPLICATION NUMBER: US/11/049,552A
CURRENT FILING DATE: 2005-02-02
NUMBER OF SEQ ID NOS: 21
SEQ ID NO 17
LENGTH: 46
TYPE: DNA
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Bxb1 attB site
Query Match 100.0%; Score 46; Length 46;
Best Local Similarity 100.0%;
Matches 46; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GGCCGGCTTGTCGACGACGGCGGTCTCCGTCGTCAGGATCATCCGG 46
||||||||||||||||||||||||||||||||||||||||||||||
Db 1 GGCCGGCTTGTCGACGACGGCGGTCTCCGTCGTCAGGATCATCCGG 46
SEQ ID NO: 16 of Padidam (2006) (US 2006/0172377 A1)
PNG
media_image9.png
192
708
media_image9.png
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The alignment of SEQ ID NO: 38 of instant application to SEQ ID NO: 16 of Padidam (2006) (US 2006/0172377 A1, US application number 11/049,552, publication date 08/03/2006) is provided below.
Title: US-18-067-214-38
Perfect score: 52
Sequence: 1 gtggtttgtctggtcaacca..........tggtgtacggtacaaaccca 52
Scoring table: IDENTITY_NUC
Gapop 10.0 , Gapext 1.0
Searched: 71052184 unique seqs, 17172728613 residues
Total number of hits satisfying chosen parameters: 142104368
Minimum DB seq length: 1
Maximum DB seq length: 40000
RESULT 1
US-11-049-552A-16
(NOTE: this sequence has 30 duplicates in the database searched.
See complete list at the end of this report)
Sequence 16, US/11049552A
Publication No. US20060172377A1
GENERAL INFORMATION
APPLICANT: Padidam, Malla
TITLE OF INVENTION: Site-Specific Serine Recombinases and Methods of Their Use
FILE REFERENCE: A01505-US
CURRENT APPLICATION NUMBER: US/11/049,552A
CURRENT FILING DATE: 2005-02-02
NUMBER OF SEQ ID NOS: 21
SEQ ID NO 16
LENGTH: 52
TYPE: DNA
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Bxb1 attP site
Query Match 100.0%; Score 52; Length 52;
Best Local Similarity 100.0%;
Matches 52; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GTGGTTTGTCTGGTCAACCACCGCGGTCTCAGTGGTGTACGGTACAAACCCA 52
||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 GTGGTTTGTCTGGTCAACCACCGCGGTCTCAGTGGTGTACGGTACAAACCCA 52
It would have been prima facie obvious for a skilled artisan to incorporate the disclosure of “invention also relates to a vector for site-specific integration of a polynucleotide sequence into the genome of an isolated eukaryotic cell, said vector comprising a polynucleotide of interest, and a second recombination attB or attP site, wherein said second recombination attB or attP site comprises a polynucleotide sequence that recombines with a first recombination attP or attB site or pseudo attP or pseudo attB site in the genome of said isolated eukaryotic cell and said recombination occurs in the presence of a site-specific recombinase selected from the group consisting of a Listeria monocytogenes phage recombinase, a Streptococcus pyogenes phage recombinase, a Bacillus subtilis phage recombinase, a Mycobacterium tuberculosis phage recombinase and a Mycobacterium smegmatis phage recombinase, provided that when the first recombination site is attB or pseudo attB, the second recombination site is attP and when the first recombination site is attP or pseudo attP, the second recombination site is attB. Preferably the recombinase is selected from the group consisting of anA118 recombinase, a SF370.l recombinase, a SPbc2 recombinase, a fRv1 recombinase, and a Bxb1 recombinase” taught by Padidam (2006) (US 2006/0172377 A1, into the teachings of Liu et al. (2020) (WO 2020/191245 A1, PCT/US2020/023727 regarding “Table 8. Large serine integrases and SSR (site-specific recombinase) target sequences”
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166
856
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to arrive at instant claims 114, and 118-122 with reasonable expectation of success because Liu et al. (2020) teaches Bxb1 being a serine-integrases and SSR target sequences whereas Padidam (2006) (US 2006/0172377 A1) teaches that SEQ ID NO: 11 being a recombinase of mycobacteriophage Bxb1, and SEQ ID NO:37 of instant application being a Bxb1 attB site where SEQ ID NO:38 of instant application being a Bxb1 attP site; and that the identity of the amino acid sequences of a Bxb1 recombinase/integration enzyme and the nucleotide sequences of a Bxb1 attB site and/or a Bxb1 attP site vary from different sources of bacteria and/or phages.
A skilled artisan would be motivated to combine the teachings Brinker et al. (2015) with the teachings of Liu et al. (2020) et al. because (i) Liu et al. (2020) et al. that the Bxb1 being a serine integrases and discloses its SSR target sequences (See Table 8), and (ii) Padidam (2006) (US 2006/0172377 A1 teaches that “Preferably the recombinase is selected from the group consisting of anA118 recombinase, a SF370.l recombinase, a SPbc2 recombinase, a fRv1 recombinase, and a Bxb1 recombinase”; and SEQ ID NO: 11 of instant application being a recombinase of mycobacteriophage Bxb1, and SEQ ID NO:37 of instant application being a Bxb1 attB site where SEQ ID NO:38 of instant application being a Bxb1 attP site.
Non-statutory 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.
(i) Claims 87-91, 95, 99-106, 109-111, and 114-122 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11,572,556 (issued on 02/07/2023; US application number 17/647,308). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-15 of U.S. Patent No. 11,572,556 are directed to the methods of using “a complex for genome editing” recited in claims 87-91, 95, 99-106, 109-111, and 114-122 of instant application.
Claims of U.S. Patent No. 11,572,556 are copied below.
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1022
712
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(ii) Claims 87-91, 95, 99-106, 109-111, and 114-122 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 11,834,658 (issued on 12/05/2023; US application number 18/066,233). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-22 of U.S. Patent No. 11,834,658 are directed to the methods of using “a complex for genome editing” recited in claims 87-91, 95, 99-106, 109-111, and 114-122 of instant application.
Claims of U.S. Patent No. 11,834,658 are copied below.
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770
844
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1066
850
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(iii) Claims 87-91, 95, 99-106, 109-111, and 114-122 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 11,827,881 (issued on 11/28/2023; US application number 18/066,223). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-16 of U.S. Patent No. 11,827,881 are directed to the systems of using “a complex for genome editing” recited in claims 87-91, 95, 99-106, 109-111, and 114-122 of instant application.
Claims of U.S. Patent No. 11,827,881 are copied below.
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490
824
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506
840
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(iv) Claims 87-91, 95, 99-106, 109-111, and 114-122 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11,952,571 (issued on 04/09/2024; US application number 18/487,744). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-16 of U.S. Patent No. 11,952,571 are directed to the systems of using “a complex for genome editing” recited in claims 87-91, 95, 99-106, 109-111, and 114-122 of instant application.
Claims of U.S. Patent No. 11,952,571 are copied below.
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1054
846
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(v) Claims 87-91, 95, 99-106, 109-111, and 114-122 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 12,195,733 (issued on 01/14/2025; US application number 18/487,610). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-13 of U.S. Patent No. 12,195,733 are directed to the systems of using “a complex for genome editing” recited in claims 87-91, 95, 99-106, 109-111, and 114-122 of instant application.
Claims of U.S. Patent No. 12,195,733 are copied below.
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346
836
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686
838
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(vi) Claim 87-91, 95, 99-106, 109-111, and 114-122 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 92-105 of copending Application No. 18/962,390 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 92-105 of copending Application No. 18/962,390 are directed to the systems of using “a complex for genome editing” recited in claims 87-91, 95, 99-106, 109-111, and 114-122 of instant application.
Claims of copending Application No. 18/962,390 (US 2025-0092390) are copied below.
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312
824
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942
838
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This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682
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