DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant's election with traverse of Group I (claims 1-2 and 8) in the reply filed on July 20, 2026 is acknowledged. The traversal is on the grounds that the claims of Group II (claims 9, 67, 79, and 82) require the same two components. This argument is found to be persuasive. Therefore, the claims of Group II will be rejoined with elected Group I. Claims 1-2, 8-9, 67, 79, and 82 will be examined in their entirety. However, the Requirement for Restriction is still in effect for Groups III, IV, and V (claims 11-19,24-25,27-30,32,35-36,38-41,43,45,70,72-74,76,84,95,97,102,105,108 and 110). Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement regarding Groups III, IV, and V, this portion of the election has been treated as an election without traverse (MPEP § 818.01(a)).
Thus, the requirement is still deemed proper and is therefore made FINAL.
Claims 11-19,24-25,27-30,32,35-36,38-41,43,45,70,72-74,76,84,95,97,102,105,108 and 110 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 with regard to Groups III, IV, and V was made without traverse in the reply filed on July 20, 2026.
Claims 1-2, 8-9, 67, 79, and 82 are under examination.
Information Disclosure Statement
The Information Disclosure Statements filed October 7, 2022 (3); June 23, 2023; January 5, 2024; January 31, 2024; March 25, 2024; June 19, 2024; and August 14, 2025 have been considered.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
It is noted that the amendment to the specification filed October 7, 2022 lists the size of the ASCII text file correctly as 124,099 bytes. However, the substitute specification file August 14, 2025 incorrectly lists the size of the file as 124,009 bytes.
Claim Objections
Claims 2 and 9 are objected to because of the following informalities:
At claim 2, line 6, “ins” should be changed to “is.”
At claim 9, line 7, each occurrence of “the” should be deleted.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1, 8-9, 67, 79, and 82 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.
The claims require a CRISPR-Cas effector protein, a CRISPR-Cas system, and eukaryotic cell comprising the CRISPR-Cas system. The rejected claims thus comprises a genus of CRISPR enzymes defined as belonging to a group of CRISPR proteins, to function to cleave a target nucleic acid. To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof. The specification states that “[t]he CRISPR-Cas effector protein may be Type V CRISPR-Cas effector protein. In certain example embodiments, the CRISPR-Cas protein is CPF1 or orthologue thereof.” See paragraph [0010]. While the Specification does include a laundry list of CRISPR-Cas proteins, as a whole the Specification is directed solely to Type II Cas9 and Type V-A Cas12 (Cpf1) CRISPR-Cas systems. Further, it is impossible for one to extrapolate from the generic recitation of broad classes of CRISPR proteins the structure of any CRISPR enzyme whose application to a nucleic acid molecule would be useful for detection of target nucleic acids. The prior art does not appear to offset the deficiencies of the instant specification. The prior art teaches that CRISPR Type I, II, and III enzymes each have different structures and function in different pathways (Sorek et al., 82 Annual Review of Biochemistry 237-266 (2013), and cited in the Information Disclosure Statement filed October 7, 2022). The prior art further discloses additional CRISPR systems, which also have different structures and function in yet different pathways (Koonin et al., 37 Current Opinion in Microbiology 67-78 (2017), and cited in the Information Disclosure Statement filed October 7, 2022). Thus, the specification is not sufficient to support the broadly claimed genus of CRISPR enzymes, which are variants having different structures and functions.
The description of the limited Cas9 and Cas12 (CpfI) CRISPR system is not sufficient to support the genus of claimed CRISPR systems. Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed.” (See Vas-Cath at page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is now is claimed." (See Vas-Cath at page 1116). As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of CRISPR systems, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation or identification. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18USPQ2d 1016. Therefore, the skilled artisan would have reasonably concluded applicants were not in possession of the claimed invention for claims 14-16 and 21-24.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-2, 8-9, 67, 79, and 82 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the limitation "the unmodified protein" in line 5. There is insufficient antecedent basis for this limitation in the claim. It is suggested that “the” be changed to “a.”
Claim 1 recites the limitation “the binding site” in line 6. There is insufficient antecedent basis for this limitation in the claim. Does this refer to the binding between the guide and the CRISPR-Cas effector protein or between the guide/protein complex and a target site?
Claims 2, 8-9, 67, 79, and 82 depend from claim 1, and are therefore included in these rejections.
Claim 2 recites the limitation "the editing preference" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 8 recites the limitation "the binding property" in line 2. There is insufficient antecedent basis for this limitation in the claim. It is suggested that “the” be changed to “a.”
Claim 8 recites the limitation “the nucleic acid molecule” in lines 3, 4, and 5. There is insufficient antecedent basis for this limitation in the claim.
At claim 9, line 1, the phrase “a target locus of interest” is indefinite because it is a relative term. One practitioner might find a particular target locus to be of interest, whereas a different practitioner would not, or would find other target loci to be of interest. It is suggested that “of interest” be deleted.
At claim 67, line 4, it is not clear how the cell comprises a stem cell or stem cell line. It is suggested that “comprises” be changed to “is.”
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
In the present instance, claim 2 recites the broad recitation “engineered CRISPR-Cas effector protein,” and the claim also recites “preferably, wherein the CRISPR-Cas effector protein is a Class V CRISPR-Cas effector protein” and “preferably, wherein the Class V CRISPR-Cas effector protein is Cpf1 or an orthologue thereof,” which are the narrower statements of the range/limitation. The claims are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
In the present instance, claim 2 recites the broad recitation “the at least one modification increases formation of one or more specific indels,” and the claim also recites “optionally, wherein the at least one modification i[n]s in a C-terminal Ruv C like domain, a N-terminal alpha-helical region, a mixed alpha and beta region, or a combination thereof,” and “optionally, wherein the at least one modification results in insertion of an A adjacent to an A, T, G, or C in a target region, insertion of a T adjacent to an A, T, G, or C in the target region, insertion of a G adjacent to an A, T, G, or C, insertion of a C adjacent to an A, T, C, or G, or a combination thereof,” which are the narrower statements of the range/limitation. The claims are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
In the present instance, claim 67 recites the broad recitation “a eukaryotic cell comprising the system of claim 9,” and the claim also recites “preferably wherein the cell is an in vitro, ex vivo, or in vivo host cell or cell line or progeny thereof,” “optionally, wherein the cell comprises a stem cell or stem cell line,” “optionally, wherein the cell is an animal or plant cell,” and “preferably a human cell,” which are the narrower statements of the range/limitation. The claims are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
In the present instance, claim 79 recites the broad recitation “for use in therapy,” and the claim also recites “preferably, wherein said therapy is for gene or genome editing, or gene therapy,” and “preferably, wherein said therapy is for the treatment of one or more of the following,” which are the narrower statements of the range/limitation. The claims are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 79 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 9, from which claim 79 depends, recites an engineered system for modifying a target locus of interest. Claim 79 recites only an intended use for the system, along with additional optional intended uses. Because the system of claim 79 is the same system recited in claim 9, claim 79 does not further limit claim 9.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(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.
Claim 1-2, 8-9, 67, 79, and 82 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (Zhang I, PCT Patent Application Publication No. WO 2015/089364, published June 18, 2015, and cited in the Information Disclosure Statement filed October 7, 2022), see the entire document.
Regarding claim 1, Zhang I discloses CRISPR-Cas effector proteins complexed with a guide molecule (paragraph [0020]. Zhang I discloses that the effector protein is Cas9 and can be modified (paragraph [0067]). Zhang I discloses that the Cas9 can be optimized (i.e., modified) to enhance function, which is interpreted as including enhanced binding or editing preferences (paragraph [0068]).
Regarding claim 2, Zhang I discloses that Cas9 mediates indel formation (paragraph [0091]).
Regarding claim 8, Zhang I discloses that the Cas9 can be mutated at a variety of positions, which can turn the Cas9 into a nickase, which is interpreted as alteration of the binding property of the protein (paragraph [0069]).
Regarding claim 9, Zhang I discloses a system comprising a guide molecule or polynucleotide encoding the guide molecule and the CRISPR-Cas effector (Cas9) protein or polynucleotide encoding the Cas9 (paragraphs [0008]-[0010]).
Regarding claim 67, Zhang I discloses a eukaryotic cell comprising the CRISPR-Cas system (paragraphs[0009]-[0012]). While optional, Zhang I does disclose that the cell can be in vivo, ex vivo or in vitro (paragraph [0075]). Zhang I discloses that the cell can be a stem cell, an animal cell, a plant cell, or a human cell (paragraphs [0011] and [0075]).
Regarding claim 79, Zhang I discloses a system comprising a guide molecule or polynucleotide encoding the guide molecule and the CRISPR-Cas effector (Cas9) protein or polynucleotide encoding the Cas9 (paragraphs [0008]-[0010]). It is noted that therapy is an intended use, and that the therapy can be for gene therapy or treatment of a variety of diseases or conditions (paragraphs [0020 [0079], [0080]).
Regarding claim 82, it is noted that claim 82 is product-by-process claims. Therefore, the claim is being interpreted as encompassing any cell that includes a CRISPR-Cas system. Zhang I discloses a eukaryotic cell comprising the CRISPR-Cas system (paragraphs[0009]-[0012]). While optional, Zhang I does disclose that the cell can be in vivo, ex vivo or in vitro (paragraph [0075]). Zhang I discloses that the cell can be a stem cell, an animal cell, a plant cell, or a human cell (paragraphs [0011] and [0075]).
Zhang I discloses each and every limitation of claims 1-2, 8-9, 67, 79, and 82. Therefore, Zhang I anticipates claims 1-2, 8-9, 67, 79, and 82.
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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-2, 8-9, 67, 79, and 82 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 11,149,267.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘267 patent claims a method of developing or designing a CRISPR-Cas system-based therapy/therapeutic by selecting target sequences that are not off-target sites. While the ‘267 patent does not explicitly claim the CRISPR-Cas effector protein, guide molecule, systems comprising the protein and guide, and cells comprising the system, the ‘267 patent does claim methods that employ each of the product claims of the instant application. Thus, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the instantly claimed proteins, guides, systems, and cells could be used in the method claimed by the ‘267 patent with a predictable and reasonable expectation of success.
Claims 1-2, 8-9, 67, 79, and 82 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 11,352,647.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘647 patent claims a method of developing or designing a CRISPR-Cas system-based therapy/therapeutic by selecting target sequences that are not off-target sites. While the ‘647 patent does not explicitly claim the CRISPR-Cas effector protein, guide molecule, systems comprising the protein and guide, and cells comprising the system, the ‘647 patent does claim methods that employ each of the product claims of the instant application. Thus, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the instantly claimed proteins, guides, systems, and cells could be used in the method claimed by the ‘647 patent with a predictable and reasonable expectation of success.
Claims 1-2, 8-9, 67, 79, and 82 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 18, 24, and 26 of U.S. Patent No. 12,559,774.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘774 patent and the instant application claims systems comprising a CRISPR-Cas protein and a guide molecule. While the ‘774 patent does not explicitly claim the CRISPR-Cas effector cells comprising the system, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that both the instantly claimed proteins, guides, systems, and those of the ‘774 patent could be introduced into cells, as claimed by the instant application, in order to provide for gene editing and/or therapy.
Claims 1-2, 8-9, 67, 79, and 82 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 156-157 and 161-163 of copending Application No. 16/325,892 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘892 application claims an isolated eukaryotic cell prepared by a method of developing or designing a CRISPR-Cas system-based therapy/therapeutic where any target sequences from a set of candidate target sequences having off-target candidate in haplotypes that occur in at least 0.1% of a population to define a final target sequences set. The Instant application claims CRISPR-Cas systems and cells comprising those systems. In addition, both the ‘892 application and the instant application claim targeting of genes associated with a blood disease or disorder, including sickle cell anemia and β-thalassemia.
It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to determine the selection of the target sequences, the effector protein, type of guide, delivery system, functionality, and/or off-target loci because this will all enable one of ordinary skill in the art to best be able to design or develop a desired CRISPR-Cas system therapeutic based on the sequences to be targeted.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 8-9, 67, 79, and 82 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2-21 of copending Application No. 19/028,841 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘841 application and the instant application claim a CRISPR-Cas system comprising a Cas protein and a guide molecule. While the ‘841 application does not explicitly claim a cell comprising the systems, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the system of the ‘841 application could be introduced into cells, as claimed by the instant application, in order to provide for gene editing and/or therapy.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 8-9, 67, 79, and 82 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2-21 of copending Application No. 19/029,037 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘037 application and the instant application claim a CRISPR-Cas system comprising a Cas protein and a guide molecule. While the ‘037 application does not explicitly claim a cell comprising the systems, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the system of the ‘037 application could be introduced into cells, as claimed by the instant application, in order to provide for gene editing and/or therapy.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 8-9, 67, 79, and 82 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 23-55 of copending Application No. 19/709,847 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘847 application and the instant application claim CRISPR-Cas systems comprising a Cas protein and a guide molecule, as well as eukaryotic cells comprising the system. The ‘847 application and the instant application claim systems and the cells can be engineered to have mutations, such that properties of the system can be altered. Therefore, the claims are not deemed to be patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Hsu et al. (157(6) Cell 1262-1278 (2014), and cited in the Information Disclosure Statement filed October 7, 2022) disclose a CRISPR-Cas9 system where the Cas9 can be guided to specific locations within genomes (abstract). Hsu discloses that off-target effects can be seen where the Cas9 can bind to off-target loci (page 1270, column 1, second full paragraph). Hsu discloses that these off-target effects can be computationally determined (page 1270, column 2, first full paragraph). Hsu discloses that off-target effects can be reduced (page 1269, column 2, second full paragraph and paragraph bridging pages 1270 and 1271). Regarding claims 21 and 24, Hsu discloses that the CRISPR-Cas9 system can provide for modified cells where the cells are associated with a genetic disease or disorder, including sickle-cell anemia (a blood disorder) (page 1274, column 2 to page 1275 column 1).
Wang et al. (U.S. Patent Application Publication No. 2016/0251648, published September 1, 2016, filed April 28, 2016, and claiming priority to PCT Patent Application No. PCT/US14/62558, filed October 28, 2014 and U.S. Provisional Patent Application Nos. 61/961,980; 61/963,643; and 62/069,243, filed October 28, 2013; December 9, 2013; and October 27, 2014) disclose a CRISPR-Cas9 system where the Cas9 can be guided to specific locations within genomes (paragraph [0045]). Wang discloses that off-target effects can be seen where the Cas9 can bind to off-target loci (paragraphs [0087]-[0092]). Wang discloses that these off-target effects can be computationally determined (paragraph [0011]). Wang discloses modified cells where off-target effects are reduced (paragraph [0089]). Wang discloses that the degree of complementarity between the guide and the target is greater than 94.5% (paragraphs [0140]). Wang discloses that the CRISPR-Cas9 system can provide for modified cells where the cells are associated with a genetic disease or disorder, including cancer (paragraph [0130]).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NANCY J LEITH whose telephone number is (313)446-4874. The examiner can normally be reached Monday - Thursday 8:00 AM - 6:30 PM.
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NANCY J. LEITH
Primary Examiner
Art Unit 1636
/NANCY J LEITH/Primary Examiner, Art Unit 1636
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