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 .
Priority
This Application is a Continuation from Application No. 17/139,678 filed 12/31/2020, which is a Continuation of Application No. 17/020,215 filed 09/14/2020, a Continuation of Application No. 16/680,104 filed 11/11/2019, which is also a Continuation of PCT/US2019/022375 dated 03/14/2019. Applicant’s claim to priority from earliest Provisional Application no. 62/642,919 dated 03/14/2018 is hereby acknowledged.
Election/Restrictions
Applicant’s election without traverse of Invention Group I (claims 1-29, drawn to an engineered, non-naturally occurring Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated Cas system and a cell comprising the system), Species A-I(2) + II(7) and Species B(1) + (2) + (3) + (5), in the reply filed on 10/08/2025 is acknowledged.
Claims 5-7, 9, 16 and 30-33 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/08/2025.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Application Status
Preliminary amendments to claims filed 10/08/2025 are hereby acknowledged. Claims 1-33 are pending. Claims 7 and 14 are currently amended. Claims 5-7, 9, 16 and 30-33 are withdrawn from consideration after restriction/election.
Therefore, claims 1-4, 8, 10-15, 17-29 are under examination in this office action.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 12/20/2021 and 10/08/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
However, the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892 or listed on a submitted IDS, they have not been considered.
Drawings
The Drawing Replacement sheets and Supplemental file with higher quality and definition filed 12/20/2021 are hereby acknowledged and are acceptable.
Specification
-The disclosure is objected to because of the following informalities: Some sequences IDs provided in Table 4 (examples: SEQ ID NO: 3, pages 83 and 84 and SEQ ID NO: 5, pages 87-88) are in duplicate.
Appropriate correction is required.
The use of the terms “EMD-Millipore”, “Genscript”, “New England
Biolabs”, “Agilent”, “Lucigen”, “NEBNext High Fidelity 2x PCR Master Mix”, “NEB Golden Gate Assembly Mix”, “Bio-rad”, “Fisher”, “Alfa Aesar”, “ lllumina”, “E. cloni”, “Biomatters”, “NEBNext Multiplex” Small RNA Library Prep Set for lllumina, “Nextseq 550”, “Geneious 11.0.2” , “Amicon Ultra-15 Centrifugal Units”, “Qubit” protein assay, “Gel Doc EZ”, “NEBNEXT Hifi 2x master mix”, “HiScribe T7 Quick High Yield RNA” kit, “Direct-zol”, “Ribo-Zero”, “RNA Clean & Concentrator-5”, which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms 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.
Claim Rejections - 35 USC § 101
35 U.S.C. §101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-4, 8, 10-15, 17-18, 20-23, and 26-27 are rejected under 35 U.S.C. § 101 because the claimed invention is directed to a naturally-occurring product without significantly more.
Regarding claim 1, it recites a “Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated (Cas) system comprising:
An RNA guide or a nucleic acid encoding the RNA guide, wherein the RNA guide comprises a direct repeat sequence and a spacer sequence, wherein the direct repeat sequence comprises 5’-CCGUCNNNNNNUGACGG-3’ (SEQ ID NO: 202), wherein N is any nucleobase; and
A CRISPR-Cas effector protein or a nucleic acid encoding the CRISPR-Cas effector protein, wherein the CRISPR-Cas effector protein binds to the RNA guide, and wherein the spacer sequence binds to a target nucleic acid.”
Therefore, Applicant is claiming a product or composition.
Subject Matter Eligibility Test for Products and Processes
Step 1 - Is the Claim to a Process, Machine, Manufacture or Composition of Matter? YES.
Claim 1 is drawn to a composition of matter as described above.
Step 2A, Prong One - Does the Claim Recite an Abstract Idea, Law of Nature, or Natural Phenomenon? YES.
According to Applicant’s disclosure, on page 31, last paragraph, “[I]n some embodiments, a set of genomic sequences is obtained from genomic or metagenomic databases. The databases comprise short reads, or contig level data, or assembled scaffolds, or complete genomic sequences of organisms. Likewise, the database may comprise genomic sequence data from prokaryotic organisms, or eukaryotic organisms, or may include data from metagenomic environmental samples. Examples of database repositories include the National Center for Biotechnology Information (NCB]) RefSeq, NCBI GenBank, NCBI Whole Genome Shotgun (WGS), and the Joint Genome Institute (JGI) Integrated Microbial Genomes (IMG)”.
Applicant further states in Example 1, page 77, that “[T]his protein family describes a large single effector associated with CRISPR systems found in uncultured metagenomic sequences collected from freshwater environments (Table 3).” Applicant confirms that CLUST.029130 (type V-I) effectors designated Cas 12i include the exemplary proteins detailed in Tables 3 and 4.
Claim 1 recites SEQ ID NO: 202, which is a consensus sequence for guide RNAs used and recognized by Cas12i. Exemplary of direct repeat sequences for these naturally occurring system are shown in Table 5 (see page 77). Absent evidence of the contrary, since guide RNAs sequences were isolated from a particular source, it is expected that the sequence occurs naturally in the source organism.
Claim 4 recites SEQ ID NO: 10 or a sequence with at least 95% sequence identity with SEQ ID NO: 10. Table 5A provides exemplary of sequences that are naturally occurring, i.e. SEQ ID NO: 5 and direct repeats that are working with the effector isolated (see page 90). Absent evidence of the contrary, since the effector protein sequences were isolated from a particular source, it is expected that the sequence of direct repeat within a guide RNA/ an RNA transcript recognized by the effector protein occurs naturally in the source organism as well.
Claim 8 recites SEQ ID NO: 101 which appears on page 95 of Specification as “a mature crRNA”. Absent evidence of the contrary, since the Type V-I CRISPR-Cas system containing Cas12i2 is a naturally isolated system, it is expected that the sequence of a mature crRNA for this effector occurs naturally in the source organism as well.
Claim 15 recites SEQ ID NO: 5 which appears in Table 4 as one of the naturally occurring Cas12i effector protein, isolated from freshwater environment.
Therefore, the claimed CRISPR system is interpreted as referring to a naturally occurring system.
Regarding claim 1 reciting "[A]n engineered, non-naturally occurring Clustered Regularly Interspaced Short Palindromic Repeat (CRISP)-associated (Cas) system", MPEP 2106 states" It is important to keep in mind that product of nature exceptions include both naturally occurring products and non-naturally occurring products that lack markedly different characteristics from any naturally occurring counterpart. See, e.g., Ambry Genetics, 774 F.3d at 760, 113 USPQ2d at 1244 ("Contrary to Myriad's argument, it makes no difference that the identified gene sequences are synthetically replicated. As the Supreme Court made clear, neither naturally occurring compositions of matter, nor synthetically created compositions that are structurally identical to the naturally occurring compositions, are patent eligible."). Thus, a synthetic, artificial, or non-naturally occurring product such as a cloned organism or a human-made hybrid plant is not automatically eligible because it was created by human ingenuity or intervention.
Step 2A, Prong Two - Does the Claim Recite an Additional Elements that Integrate the Judicial Exception into a Practical Application? NO
The Supreme Court has long distinguished between principles themselves, which are not patent eligible, and the integration of those principles into practical applications, which are patent eligible. However, absent are any additional elements recited in the claim beyond the judicial exception(s) which integrate the exception into a practical application of the exception.
The phrase "integration into a practical application" requires an additional element or a combination of additional elements in the claim to apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception, such that it is more than a drafting effort designed to monopolize the exception.
Regarding step 2A, prong two, this judicial exception is not integrated into a practical application because the CRISPR-Cas effector proteins and RNA molecules are deemed to be products of nature/naturally-occurring products. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because, whether isolated or not, such CRISPR-Cas effector proteins, and guide molecules are deemed to fall under the judicial exception of natural products, whether engineered or not, and as such, are not patent-eligible subject matter pursuant to the Supreme Court decision in Association for Molecular Pathology v. Myriad Genetics, Inc., -- U.S. --(June 13, 2013). In Myriad, the Supreme Court considered the patent eligibility of several claims directed to isolated DNA related to the human BRCA1 and BRCA2 cancer susceptibility genes. The Supreme Court held that certain of Myriad Genetics' claims to isolated DNA are not patent-eligible, because they read on isolated naturally-occurring DNA that is a "product of nature." The Court held that isolating a "gene from its surrounding genetic material is not an act of invention." The Supreme Court held that other claims are patent eligible, because they are limited to cDNA, which is a type of man-made DNA composition that is not naturally occurring. The Court held that "cDNA is not a 'product of nature' and is patent eligible under §101."
There are no further/additional steps which applies either the identified judicial exceptions into a practical application. Thus, the claims do not provide for any element/step that integrates the law of nature into a practical application.
Step 2B - Does the Claim Recite Additional Elements that Amount to Significantly More than the Judicial Exception? NO
The Supreme Court has identified a number of considerations for determining whether a claim with additional elements amounts to "significantly more" than the judicial exception(s) itself. The claims as a whole is evaluated as to whether it amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim. M.P.E.P. 2106.05. However, the additional elements, individually and in combination, do not amount to "significantly more".
Under the Step 2B analysis, claim 1 provides no additional "physical" elements/steps that would distinguish the naturally occurring product from a synthetic product. The “wherein” clauses are drawn to naturally inherent function of the product.
As explained with respect to Step2A Prong Two, the recitations "An engineered, non-naturally occurring” in claim 1 does not indicate a markedly different product than the naturally occurring product.
The recitations of “SEQ ID NO: 202” (claim 1), “SEQ ID NO: 10” (claim 4), “SEQ ID NO: 101” (claim 8), “SEQ ID NO: 5” (claim 15), do not exclude the naturally occurring products listed in Table 4 and Examples 1-3.
Regarding claims 2-3, and 10-13, there is no specific indication that the recited limitations do not occur naturally, as these limitations are drawn to characteristics that are inherent to the naturally occurring product for its function.
Regarding claims 10-11, Hillary (Hillary, V.E. et al. “A review on the mechanism and applications of CRISPR/Cas9/Cas12/Cas13/Cas14 proteins utilized for genome engineering”. Molecular Biotechnology, Vol. 65 (2023), pp: 311-325; cited on IDS filed 10/08/2025) teaches that Cas12 effector protein can use spacers of different lengths (see page 317), and on page 319, in Figure 6, the effector protein uses a 22-28 nt spacer. On page 320, Figure 7, Hillary teaches a 30 nt spacer.
Regarding claim 12, in figure 4, Hillary teaches that some of the 17bp spacer sequence is complementary to the target sequence, and in figure 6, the Cas13a cleaves ssRNA upon recognizing the target sequence (22-28 nt) complementary to the crRNA spacer.
Regarding claim 13, the limitation is a negative limitation that does not further add limitation to indicate a non-naturally occurring product. Hillary teaches that “[A]s alternative to Cas9 and Cas10, the Cas12 protein enhanced genome-editing efficiency by targeting only T-rich motifs without utilizing tracrRNA (see page 312, left column, lines 18-20).
Regarding claim 14, the limitations are descriptions of suitable RuvC domains (Figure 2B) which include the naturally occurring proteins isolated from environmental samples taught in Specification in Table 4.
Regarding claims 17-18, Hillary teaches preferences of some effector proteins for T-rich PAM (adjacent protospacer motif) sequence that encompasses 5’-TTN-3’ sequence (see page 314, Table 2).
Regarding claim 20, Hillary teaches that cas12 protein is an effector RNA-guided DNA endonuclease that is an alternative to the Cas9 protein for genome editing (see page 317, left column, “Cas12 protein” paragraph), therefore, the effector protein comes naturally with multiple domains, and one necessary for base-editing.
Regarding claims 21, and 26-27, the claims are broad and the BRI (broad and reasonable interpretation) includes evolutionary processes adapting, i.e. codon-optimizing, the effector protein to a specific cell as taught by Shmakov (Shmakov, S. et al. “Diversity and evolution of class 2 CRISPR-Cas system”. Nature Review Microbiology, Vol. 15(3) (2017), pp: 169-182; cited on IDS filed 10/08/2025) (see “[A]bstract” section). The cells taught by Hillary in Table 2 are bacteria/prokaryotic cells.
Regarding claims 22 and 23, the BRI of the claims includes vectors such as naturally occurring chromosomes, that also comprise promoters and other elements necessary for transcription/expression of the CRISPR Cas effector protein.
Absent from the claims is a limitation(s) that has more than a nominal relationship to the judicial exception. There is no limitation(s) that integrates the recited judicial exception into a practical application, such that the claim is not directed to the judicial exception.
Thus, when viewed both individually and as an ordered combination, the claimed
elements/steps in addition to the identified judicial exception are found insufficient to supply an inventive concept because the elements/steps are considered conventional and specified at a high level of generality. The claim limitations do not transform the naturally-occurring product that they recite into patent-eligible subject matter because the claims simply detail to the practitioner characteristics associated with inherent activity.
Here, the claims read on the judicial exception of naturally occurring CRISPR-associated effector proteins, Cas proteins, and guide molecules. It is well-known CRISPR-associated transposase proteins, Cas proteins, and guide molecules are found in Nature. For example, CRISPR-associated effector proteins, Cas proteins, and guide molecules are well-known and can be isolated from a variety of bacteria (see, e.g., Shmakov and Hillary (both cited above). Thus, the claimed CRISPR-associated transposase proteins, Cas proteins, and guide molecules do not differ significantly from the judicial exception of naturally occurring products.
Accordingly, the claims do not qualify as patent-eligible subject matter.
Claims 26-29 are rejected under 35 U.S.C. § 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. §101).
The claims recite “ A cell comprising the system of claim 1”, wherein the cell is “ a prokaryotic cell or a eukaryotic cell”, “ a mammalian cell or a plant cell”, and “ a human cell”.
The instant specification discloses that “In some embodiments of any of the systems provided herein, the system is within a cell (e.g., a eukaryotic cell (e.g., a mammalian cell) or a prokaryotic cell (e.g., a bacterial cell))”, (page 7, lines 19-20).
The instant specification discloses that “These can be carried out ex vivo or in vitro methods”. The specification further discloses that “the methods described herein do not modify the germ line genetic identity of a human being, which is interpreted as being administered to a human being” (page 7, lines 21-25).
However, claims 26-29 as written, are deemed to encompass human cells and tissues, even germ line cells, which are present or intended to be present in a human organism, and which is non-statutory subject matter. As such the recitation of the limitation "isolated" cell would be remedial. See 1077 Off Gaz.Pat. Office 24 (April 21, 1987).
Non-Statutory Double Patenting
The non-statutory 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 non-statutory 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 non-statutory 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 non-statutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 10-14 and 17-29 are provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claims 1-3, 7, 9-15, 17-18, 20-21 of the co-pending application 17/020,414.
Regarding claims 1, and 26-27, claim 1 of co-pending application 17/020,414 claim “an engineered, non-naturally occurring Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) - associated (Cas) system comprising:(a) an RNA guide or a nucleic acid encoding the RNA guide, wherein the RNA guide comprises a direct repeat sequence and a spacer sequence; and (b) a CRISPR-Cas effector protein or a nucleic acid encoding the CRISPR-Cas effector protein, wherein the CRISPR-Cas effector protein comprises the amino acid sequence with at least 95% identity to SEQ ID NO:14 or SEQ ID NO: 16, wherein the CRISPR-Cas effector protein binds to the RNA guide, and wherein the spacer sequence is capable of hybridizing to a target nucleic acid in a eukaryotic cell.”
MPEP 804(II)(B)(1) states,” The portion of the specification of the reference that describes subject matter that falls within the scope of a reference claim may be relied upon to properly construe the scope of that claim. In particular, when ascertaining the scope of the reference’s claim(s) to a compound, the examiner should consider the reference’s specification, including all of the compound’s uses that are disclosed. See Sun Pharm. Indus., 611 F.3d at 1386-88, 95 USPQ2d at 1801-02 (emphasis added).”
SEQ ID NOs: 14 and 16 in co-pending application 17/020,414 are species in the claimed genus; both co-pending applications teaches these SEQ ID Nos in Table 4, to be used as a CRISPR-Cas effector proteins that recognize and bind to RNA guide comprising SEQ ID NO: 202 as direct repeat sequence (see Table 4, and see page 49, last paragraph).
Regarding claims 10-11, claim 7 of co-pending application 17/020,414 claims the spacer sequence between 15 and 47 nt in length.
claim 8 of co-pending application 17/020,414 claims the spacer sequence nucleotide length between 24 and 38.
Regarding claim 12, claim 9 of co-pending application 17/020,414 claims the target nucleic acid comprises a sequence complementary to a nucleotide sequence in the spacer sequence.
Regarding claim 13, claim 2 of co-pending application 17/020,414 claims the system does not include a tracrRNA.
Regarding claim 14, claim 3 of co-pending application 17/020,414 claims the same elements of claim 14.
Regarding claims 17-18, claim 10 of co-pending application 17/020,414 claims the system of claim 1, wherein the CRISPR-Cas effector protein recognizes a protospacer adjacent motif (PAM) sequence, wherein the PAM sequence comprises a nucleotide sequence set forth as 5'-TTN-3', wherein N is any nucleotide.
Regarding claim 19, claim 11 of co-pending application 17/020,414 claims the system of claim 1, wherein the CRISPR-Cas effector protein further comprises at least one nuclear localization signal (NLS), at least one nuclear export signal (NES), or at least one NLS and at least one NES.
Regarding claim 20, claim 12 of co-pending application 17/020,414 claims the CRISPR-Cas effector protein further comprises a peptide tag, a fluorescent protein, a base-editing domain, a DNA methylation domain, a histone residue modification domain, a localization factor, a transcription modification factor, a light-gated control factor, a chemically inducible factor, or a chromatin visualization factor.
Regarding claim 21, claim 13 of co-pending application 17/020,414 claims the nucleic acid encoding the CRISPR-Cas effector protein is codon-optimized for expression in a cell.
Regarding claim 22, claim 14 of co-pending application 17/020,414 claims wherein the nucleic acid encoding the CRISPR-Cas effector protein is operably linked to a promoter.
Regarding claim 23, claim 15 of co-pending application 17/020,414 claims the nucleic acid encoding the CRISPR-Cas effector protein is in a vector.
Regarding claim 24, claim 15 of co-pending application 17/020,414 claims the nucleic acid encoding the CRISPR-Cas effector protein is in a vector.
MPEP 804(II)(B)(1) states,” The portion of the specification of the reference that describes subject matter that falls within the scope of a reference claim may be relied upon to properly construe the scope of that claim. In particular, when ascertaining the scope of the reference’s claim(s) to a compound, the examiner should consider the reference’s specification, including all of the compound’s uses that are disclosed. See Sun Pharm. Indus., 611 F.3d at 1386-88, 95 USPQ2d at 1801-02 (emphasis added).”
In co-pending application 17/020,414, Applicant discloses in the Specification, on
page 10, that “[I]n some embodiments, the vectors included in the systems are viral vectors (e.g., retroviral vectors, lentiviral vectors, adenoviral vectors, adeno-associated vectors, and herpes simplex vectors. In some embodiments, the vectors included in the system are phage vectors”. These elements encompassed by the claim 15 limitations in co-pending application 17/020,414, are recited in instant claim 50.
Regarding claim 25, claim 17 of co-pending application 17/020,414 claims the system is present in a delivery system comprising a nanoparticle, a liposome, an exosome, a microvesicle, or a gene-gun.
Regarding claim 26, claim 18 of co-pending application 17/020,414 claims a cell comprising the system of claim 1.
Regarding claim 27, claim 18 of co-pending application 17/020,414 claims a cell comprising the system of claim 1. MPEP 804(II)(B)(1) states,” The portion of the specification of the reference that describes subject matter that falls within the scope of a reference claim may be relied upon to properly construe the scope of that claim. In particular, when ascertaining the scope of the reference’s claim(s) to a compound, the examiner should consider the reference’s specification, including all of the compound’s uses that are disclosed. See Sun Pharm. Indus., 611 F.3d at 1386-88, 95 USPQ2d at 1801-02 (emphasis added).” Co-pending application 17.020,414 teaches that the cell can be eukaryotic or prokaryotic (see page 10, line 20).
Regarding claim 28, claim 20 of co-pending application 17/020,414 claims “the cell is a mammalian cell or a plant cell”.
Regarding claim 29, claim 21 of co-pending application 17/020,414 claims “wherein the cell is a human cell”.
Claims 1, 3, 10-14, and 17-29 are provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claims 32-33, 36, 38-43, 45-52 of the co-pending application 17/020,215.
Regarding claim 1, claim 32 of co-pending application 17/020,215
claims “An engineered, non-naturally occurring Clustered Regularly lnterspaced Short Palindromic Repeat (CRISPR) - associated (Cas) system comprising:
(a) an RNA guide or a nucleic acid encoding the RNA guide, wherein the RNA guide comprises a direct repeat sequence and a spacer sequence; and
(b) a CRISPR-Cas effector protein or a nucleic acid encoding the CRISPR-Cas effector protein, wherein the CRISPR-Cas effector protein comprises the amino acid sequence set forth in SEQ ID NO: 16, wherein the CRISPR-Cas effector protein binds to the RNA guide, and wherein the spacer sequence binds to a target nucleic acid”. SEQ ID NO: 16 is a species of the claimed genus. MPEP 804(II)(B)(1) states,” The portion of the specification of the reference that describes subject matter that falls within the scope of a reference claim may be relied upon to properly construe the scope of that claim. In particular, when ascertaining the scope of the reference’s claim(s) to a compound, the examiner should consider the reference’s specification, including all of the compound’s uses that are disclosed. See Sun Pharm. Indus., 611 F.3d at 1386-88, 95 USPQ2d at 1801-02 (emphasis added).”
Regarding claim 3, claim 36 of co-pending application 17/020,215 claims the same elements of claim 3 for the direct repeat sequence.
Regarding claim 10, co-pending application 17/020,215 claims the spacer
sequence between 15 and 47. Claim 10 is anticipated by claims 38, 39, 40, and 41 of co-pending application 17/020215 because the spacer sequence nucleotide length
between "19 and 41" claimed in claims 39 and 41 of the co-pending application and
spacer sequence nucleotide length between "20 and 38" claimed in claims 40 and 42
are within the range of spacer sequence nucleotide length between "15 and 47" of the
instant application. See claims 38-41.
Regarding claim 11, co-pending application 17/020,215 claims the spacer
sequence nucleotide length between 20 and 38. The instant application claims a spacer
sequence nucleotide length between 24 and 38 or between 20 and 33, which overlaps with the claimed nucleotide lengths of the co-pending application. Since the claimed range and the ranges of the co-pending application overlap, a prima facie case of obviousness exists. See claims 38-41.
Regarding claim 12, co-pending application 17 /020,215 claims the target nucleic acid comprises a sequence complementary to a nucleotide sequence in the spacer sequence. See claim 42.
Regarding claim 13, claim 33 of co-pending application 17/020,215 claims the system does not include a tracrRNA.
Regarding claim 14, co-pending application 17/020,215 claims SEQ ID NO: 16
which comprises the amino acid sequence: 893-TSHQDPF-899, X1 is T, X4 is Q, X6 is P and X7 is F. SEQ ID NO: 200 of the instant application comprises the same amino acid sequence. See claim 32.
Regarding claims 17-18, claim 43 of co-pending application 17 /020,215 claims the system of claim 32, wherein the CRISPR-Cas effector protein recognizes a protospacer adjacent motif (PAM) sequence, wherein the PAM sequence comprises a nucleotide sequence set forth as 5'-TTN-3', wherein N is any nucleotide.
Regarding claim 19, claim 45 of co-pending application 17 /020,215 claims the system of claim 32, wherein the CRISPR-Cas effector protein further comprises at least one nuclear localization signal (NLS), at least one nuclear export signal (NES), or at least one NLS and at least one NES.
Regarding claim 20, claim 46 of co-pending application 17/020,215 claims the CRISPR-Cas effector protein further comprises a peptide tag, a fluorescent protein, a base-editing domain, a DNA methylation domain, a histone residue modification domain, a localization factor, a transcription modification factor, a light-gated control factor, a chemically inducible factor, or a chromatin visualization factor.
Regarding claim 21, co-pending application 17 /020,215 claims the nucleic acid encoding the CRISPR-Cas effector protein is codon-optimized for expression in a cell. See claim 47.
Regarding claim 22, co-pending application 17 /020,215 claims wherein the nucleic acid encoding the CRISPR-Cas effector protein is operably linked to a promoter. See claim 48.
Regarding claims 23-24, claims 49-50 of co-pending application 17 /020,215 claim the nucleic acid encoding the CRISPR-Cas effector protein is in a vector and recite different type of vectors.
Regarding claim 25, claim 51 of co-pending application 17/020,215 claims the system is present in a delivery system comprising a nanoparticle, a liposome, an exosome, a microvesicle, or a gene-gun.
Regarding claim 26 , claim 52 of co-pending application 17/020,215 claims A cell comprising the system of claim 32.
Regarding claims 27-29, co-pending application 17/020,215 claims a cell.
The co-pending application's specification teaches that "a cell" is eukaryotic, prokaryotic, bacterial, mammalian, see e.g. pp. 7, 8, 9, 10. The scope of cell classifications in the instant claims covers human, mammalian, bacterial, plant, eukaryotic, and prokaryotic cells. Therefore, given the information in the co-pending application's specification, claims 27-29 are prima facie obvious evidenced by applicant's inclusion of a cell. See claim 52.
MPEP 804(11)(8)(1) states," The portion of the specification of the reference that describes subject matter that falls within the scope of a reference claim may be relied upon to properly construe the scope of that claim. In particular, when ascertaining the scope of the reference's claim(s) to a compound, the examiner should consider the reference's specification, including all of the compound's uses that are disclosed. See Sun Pharm. Indus., 611 F.3d at 1386-88, 95 USPQ2d at 1801-02 (emphasis added)."
Summary
Claims 1, are rejected under 35 U.S.C. § 101. Claims 1, 3, 10-14 and 17-29 are provisionally rejected on the ground of non-statutory double patenting.
SEQ ID NOs: 5 and SEQ ID NO: 101 are free of prior art. These sequences are describing residues of a new class of CRISPR Cas effector proteins, Cas12i and a specific guide RNA residues. SEQ ID NO: 5 only appears in Applicant’s co-pending applications in the Specification, not in the claims.
Shmakov teaches the evolution and early isolations of CRISPR Cas effector proteins (cited above). Hillary describes the newest Cas12 proteins being isolated in prior art (cited above). However, the closest prior art describing the newest class of Cas12i effector proteins corresponding to their functional characterization, is Yan ( Yan, W.X. et al. “Functionally diverse type V CRISPR-Cas systems.” Science, Vol. 363 (2018), pp: 88-91 cited on IDS dated 12/20/2021 as NPL# 47). This publication is also Applicant’s publication about their aggregation of 10 terabytes of sequence data and generation of database introducing the new species of putative CRISPR-Cas systems. Yan characterizes the type V Cas12 effector proteins g, h and i (see figure 1A).
Conclusion
No claim is allowed.
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/A.D./Examiner, Art Unit 1636
/NANCY J LEITH/Primary Examiner, Art Unit 1636