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 of R490Q, the combination of 5’-A-3’, SEQ ID NOs:11-12 and 111, and KRAB in the reply filed on May 11, 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Status of Claims
Claims 1-22 are pending in the instant application. Upon further consideration, the restriction requirement for dCas12f1 protein species election is withdrawn. Accordingly, 12 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species, there being no allowable generic or linking claim. Accordingly, claims 1-11 and 13-22 are under examination on the merits in the instant application.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Specification
1. The abstract is objected to because of the following informalities: The abstract as filed on October 16, 2023 is missing a period after “RNA”. See the following line:
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Appropriate correction is required.
2. The disclosure is objected to because of the following informalities: The specification does not have appropriate section titles in correct order. For instance, “MODE OF DISCLOSURE” is not compliant with 37 CFR 1.77(b).
As provided in 37 CFR 1.77(b), the specification of a utility application should include the following sections in order. Each of the lettered items should appear in upper case, without underlining or bold type, as a section heading. If no text follows the section heading, the phrase “Not Applicable” should follow the section heading:
(a) TITLE OF THE INVENTION.
(b) CROSS-REFERENCE TO RELATED APPLICATIONS.
(c) STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT.
(d) THE NAMES OF THE PARTIES TO A JOINT RESEARCH AGREEMENT.
(e) INCORPORATION-BY-REFERENCE OF MATERIAL SUBMITTED ON A READ-ONLY OPTICAL DISC, AS A TEXT FILE OR AN XML FILE VIA THE PATENT ELECTRONIC SYSTEM.
(f) STATEMENT REGARDING PRIOR DISCLOSURES BY THE INVENTOR OR A JOINT INVENTOR.
(g) BACKGROUND OF THE INVENTION.
(1) Field of the Invention.
(2) Description of Related Art including information disclosed under 37 CFR 1.97 and 1.98.
(h) BRIEF SUMMARY OF THE INVENTION.
(i) BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S).
(j) DETAILED DESCRIPTION OF THE INVENTION.
(k) CLAIM OR CLAIMS (commencing on a separate sheet).
(l) ABSTRACT OF THE DISCLOSURE (commencing on a separate sheet).
(m) SEQUENCE LISTING. (See MPEP § 2422.03 and 37 CFR 1.821 - 1.825). A “Sequence Listing” is required on paper if the application discloses a nucleotide or amino acid sequence as defined in 37 CFR 1.821(a) and if the required “Sequence Listing” is not submitted as an electronic document either on read-only optical disc or as a text file via the patent electronic system. Appropriate correction is required.
3. The disclosure is objected to because of the following informalities: The entirety of Tables 01-31 is not in black colored font/lines, thereby rendering the Tables illegible. Note that application papers must be clearly legible using black colored font text and black lines. See MPEP §608.01. Appropriate correction is required.
4. The disclosure, see page 234, is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Drawings
The drawings are objected to for the following:
1. FIG. 1 contains sequence rule non-compliant subject matter. Appropriate correction is required as instructed below.
2. FIG. 46 contains indistinguishable bar legends. See “PCSK9_gRNA_2” and “PCSK9_gRNA_3”. Appropriate correction is required.
3. FIG. 47 and FIG. 48 contain bars with different shades/colors without indicating what each of shades/colors represents. Appropriate correction is required.
4. FIG. 55 does not have a proper label for the x-axis. Appropriate correction is required.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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 – Nucleotide sequences appearing in the drawings, see FIG. 1, are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, 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.
Claim Objections
Claim 8 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 6. Note that claim 7 fails to further limit claim 1 as explained in the rejection below. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 112
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.
Claims 7 and 18 are 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 7 recites “wherein the transcriptional inhibitor Cas12f1 fusion protein further comprises at least one transcriptional inhibitor protein.” This limitation is already recited in claim 1. See lines 7-8. Hence, claim 7 fails to further limit the subject matter of claim 1.
Claim 18 recites the “wherein” limitation, which is not different and patentably distinct from what is already recited in claim 17, lines 3-6. That is, claim 18 merely recites the same limitation in different words, thereby merely repeating the same method step that is already recited in claim 17. Hence, claim 18 fails to further limit the subject matter of claim 17.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-11 and 13-22 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1-11 and 13-22 recite “wherein the dCas12f1 protein is a modified form of a wild-type Cas12f1 protein in which aspartic acid (D) which is the 326th amino acid,…arginine (R) which is the 490th amino acid,…in the amino acid sequence constituting the wild-type Cas12f1 protein is substituted with alanine (A), glutamine (Q), leucine (L), tryptophan (W), or valine (V)”. The claims do not clearly recite the “wild-type Cas12f1 protein” sequence by its amino acid sequence. As such, the specific amino acid residues at 326th, 422nd, 490th, and 510th positions within the “wild-type Cas12f1 protein” cannot be clearly ascertained, especially in light of the fact that the instant specification does not appear to clearly disclose/identify the amino acid sequence of the “wild-type Cas12f1 protein”. That is, the exact amino acid sequence of the “wild-type Cas12f1 protein” can differ and vary depending on the organism (e.g., Syntrophomonas palimitatica) from which the Cas protein is derived. See for instance Bigelyte et al. (Nature Communications, 2021, 12:6191) disclosing “SpCas12f1” derived from Syntrophomonas palimitatica and “AsCas12f1” derived from Acidibacillus sulfuroxidans. See also “UnCas12f1”, “OsCas12f1”, “PtCas12f1”, “RuCas12f1”, and “RhCas12f1” currently known in the art as disclosed by Wu et al. (Nature Chemical Biology, 2023, 19:1384-1393). See page 1385 and Figure 1b. As such, the claimed “modified form” for the “dCas12f1 protein” reads on various, different amino acid sequences depending on the different wild-type Cas12f1 proteins. Hence, the claimed “dCas12f1 protein” sequence is not definitive as ambiguously claimed without any amino acid sequence identifier.
Claims 1 and 17 recite “a, b, c are each an integer” for the sequence “represented by (UaN)bUc”. Claims 1 and 17 point out the integers represented by “a” and “b” and fail to particularly point out and distinctly claim which integer “c” represents. As such, the clear metes and bounds of the sequence formula cannot be ascertained.
Claim 1 recites the limitation "the transcriptional inhibitor protein is" in line 14. There is insufficient antecedent basis for this limitation in the claim.
Claim 10 recites “5’-UUUURUUUU-3’.” The claim fails to particularly point out and distinctly claim what “R” at position 5 represents, thereby rendering the metes and bounds of the claimed sequence unclear.
Claim 18-19 each recite the limitation "wherein the delivery" in line 1. There is insufficient antecedent basis for this limitation in the claims.
Claim 21 recites “wherein the viral vector is at least one selected from”. It is unclear whether the singular “viral vector” is meant to comprise a plurality of different viral vectors because the claim recites “at least one”.
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 1-11 and 13-22 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 instant claims are broadly drawn to a gene expression regulatory composition for inhibiting target gene expression, wherein the composition comprises a dCas12f1 protein that is modified to comprises alanine, glutamine, leucine, tryptophan, or valine at amino acid residue positions 326, 422, 490, or 510, wherein the dCas12f1 protein a part of “a transcriptional inhibitor Cas12f1 fusion protein” “that inhibits or suppresses transcription of the gene”.
The instant specification does not appear to describe a representative number of structural dCas12f1 protein variants having any one of alanine (A), glutamine (Q), leucine (L), tryptophan (W), or valine (V) at any of positions 326, 422, 490, and 510, wherein the variants have the required, claimed function of constituting a transcriptional inhibition fusion protein that inhibits or suppresses target gene transcription. The specification at best appears to describe R490A, R490Q, R490L, R490W, D510A, D510L, and D510V variants, which are shown to be highly unpredictable in providing intended target suppression as evidenced by FIG. 34 demonstrating about 8% inhibition of BRCA1 mRNA with a composition comprising D510V and “Ver4.1-BRCA1-1”, which is in stark contrast to about 38% inhibition of BRCA1 mRNA with a composition comprising D510A and “Ver4.1-BRCA1-1”. Indeed, consistent with the unpredictable nature of activity/function of the modified Cas12f1 protein as disclosed in the instant application, the relevant art by Wu et al. (Nature Chemical Biology, 2021, 17:1132-1138) reflecting the level of the pertinent knowledge as of the filing date sought in the instant application expressly discloses that the activity/function of the modified AsCas12f1 proteins cannot be predicted unless actually synthesized and tested. See page 1134 for the following: “D225A and E324A completely abolished the nuclease activity, whereas R383A and D401A retained minor nickase activity”. Moreover, it appears that the dCas12f1 protein can function as “a transcriptional inhibitor Cas12f1 fusion protein” only when it is fused to the KRAB transcription repressor, wherein the KRAB-fused transcriptional inhibitor dCas12f1 protein comprising R490A, R490Q, R490L, R490W, D510A, or D510L is not a representative number of species within the claimed fusion protein genus. In addition, it is impossible to determine whether “Ver4.1-BRCA1-1” comprises the required nucleotide sequences comprising sequentially “A”, SEQ ID NO:11, SEQ ID NO:12, and 5’-AUGCAAC with “a U-rich tail” as claimed and elected by applicant as the instant specification appears to be completely silent and devoid of the nucleotide sequence information pertaining to “Ver4.1-BRCA1-1”. It is noted that the instant specification itself does not adequately describe that differently truncated/modified gRNA sequences as claimed in the instant claims do work with the dCas12f1 variants claimed in the instant case for target transcription repression, wherein it was known in the art prior to the filing date of the instant application that the actual gene regulation activity by the truncated/modified Cas12f gRNA sequences is highly unpredictable and variable as evidenced by Kim et al. (Nature Biotechnology, published online on September 2, 2021, 40:94-102, applicant’s citation). See Figures 1e-1g. Note that the specificity of the disclosure inversely correlates with the level of unpredictability and the level of prior art knowledge in order to satisfy the written description requirement. See MPEP §2163. In the instant case, the instant specification is inadequate in fully and adequately describing that all of the recited gRNA sequences in the 5’ to 3’ direction function in providing target transcription repression when complexed within the claimed gene expression regulatory composition.
In view of the foregoing, the instant specification is insufficient and deficient in adequately describing the entire genus of the claimed subject matter in such a manner to reasonably convey that that the instant co-inventors had possession of the claimed genus as of the filing date sought in the instant application.
Claim Rejections - 35 USC § 103
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 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3-11, and 13-22 are rejected under 35 U.S.C. 103 as being unpatentable over Yamagata et al. (US 2019/0376088 A1) in view of Kim et al. (Nature Biotechnology, published online on September 2, 2021, 40:94-102, applicant’s citation) and Xu et al. et al. (Molecular Cell, 2021, 81:4333-4345, applicant’s citation).
Applicant cannot rely upon the certified copy of the foreign priority application to overcome this rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
Yamagata teaches that a CRISPR system comprising a gRNA and “a fusion protein” comprising a defective/dead/inactive Cas9 (dCas9) that is fused to a “transcription repressor” protein that is KRAB, wherein the dCas9-KRAB fusion protein is linked to a nuclear localization signal (NLS) is useful in providing “transcriptional repressor effect” in the target, which is “suppressed.” See paragraphs 0010, 0038, 0047, and 0093; claims 6-13.
Yamagata does not teach a transcriptional repressor CRISPR system comprising dCas12f1-KRAB fusion protein and the claimed gRNA comprising “A”, SEQ ID NO:11, SEQ ID NO:12, and 5’-AUGCAAC with “a U-rich tail”.
Kim teaches that Un1Cas12f1 (referred to as Cas12f) together with optimized gRNA with reduced size provides a “compact CRISPR system” enables “multiplexed and efficient genome editing” thus is useful for developing “AAV-deliverable” gene expression regulators including “transcriptional regulators”, wherein it is known in the art that “inactive Cas proteins have been fused to transcriptional regulators, thereby achieving tailored gene expression”, wherein Kim exemplifies “dCas12(D510A) fused to VP64”. See pages 94 and 100-101.
Kim discloses an engineered, reduced size guide RNA, “Cas12_ge4.0”, which is suitable and optimized for Cas12f-based genome editing with high performance. See page 95. See also Supplementary Figure 5 showing “Cas12f_ge4.0”, wherein the gRNA fully satisfies the sequence requirements set forth in claim 11.
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Xu reports “a nuclease-deactivated Cas12f (dCas12f) by introducing two mutations (D326A and D510A)”. See page 4335.
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify Yamagata’s CRISPR-dCas9-KRAB-NLS system by replacing dCas9 with Xu’s dCas12f having D510A and incorporating Kim’s Cas12f-optimized gRNA. One of ordinary skill in the art would have been motivated to do so with in order to make a transcription repressor system that is compact in size for providing CRISPR-mediated target transcription repression in a cell because making a CRISPR system comprising an inactive Cas protein fused to a transcriptional regulator including the transcription repressor KRAB was known and utilized in the art as evidenced by Yamagata, and because use of dCas12f having D510A fused to a transcription regulator protein was also practiced in the art as evidenced by Kim, who taught Cas12f provides a “compact CRISPR system” that can be developed into various AAV-vector-deliverable gene expression regulator systems, wherein D510A- or D326A-containing Cas12f was an art-recognized “nuclease-deactivated Cas12f” as corroborated by Xu. It would also have been prima facie obvious for one of ordinary skill in the art to utilize the optimized gRNA sequence of “Cas12f_ge4.0” when making and using the CRISPR-dCas12f-KRAB-NLS system for target transcription repression because the gRNA structure/sequence was deemed to provide high performance among a number of various gRNA structures/sequences screened by Kim.
Accordingly, claims 1, 3-11, and 13-22 taken as a whole would have been prima facie obvious before the effective filing date.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 4-11, and 13-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-38 of copending Application No. 18/030,418 in view of Takeda et al. (Molecular Cell, 2021, 81:558-570), Yamagata et al. (US 2019/0376088 A1), and Zhao et al. (Frontiers in Molecular Biosciences, 2021, 8:652392).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the ‘418 claims drawn to and require a composition comprising Cas12f1 and an engineered gRNA comprising the instantly claimed nucleotide sequences. See SEQ ID NOs:11, 12, and 111. It would have been obvious to replace Cas2f1 of the ‘418 claims with Takeda’s Cas12f “D326A mutant” that “did not cleave the target DNA” (See page 560) so as to make a target transcription inhibitor system because use of a defective Cas enzyme having no DNA cleavage/nickase activity in combination with a gRNA and KRAB for the purpose of repressing gene expression via the “CRISPRi transcription suppression technology” (see page 2 of Zhao) was widely known and practiced in the prior art as evidenced by Yamagata and Zhao.
Claims 1, 4-11, and 13-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of copending Application No. 18/030,575 in view of Takeda et al. (Molecular Cell, 2021, 81:558-570), Yamagata et al. (US 2019/0376088 A1), and Zhao et al. (Frontiers in Molecular Biosciences, 2021, 8:652392).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the ‘575 claims drawn to a composition comprising Cas12f1 and an engineered gRNA comprising the instantly claimed nucleotide sequences. See SEQ ID NOs:213 and 292, for instance. It would have been obvious to replace Cas2f1 of the ‘575 claims with Takeda’s Cas12f “D326A mutant” that “did not cleave the target DNA” (See page 560) so as to make a target transcription inhibitor system because use of a defective Cas enzyme having no DNA cleavage/nickase activity in combination with a gRNA and KRAB for the purpose of repressing gene expression via the “CRISPRi transcription suppression technology” (see page 2 of Zhao) was widely known and practiced in the prior art as evidenced by Yamagata and Zhao.
Claims 1, 4-11, and 13-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-33 of copending Application No. 18/030,624 in view of Takeda et al. (Molecular Cell, 2021, 81:558-570), Yamagata et al. (US 2019/0376088 A1), and Zhao et al. (Frontiers in Molecular Biosciences, 2021, 8:652392).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the ‘624 claims drawn to and require a composition comprising Cas12f1 and an engineered gRNA comprising the instantly claimed nucleotide sequences. See SEQ ID NOs:10, 159, and 110. It would have been obvious to replace Cas2f1 of the ‘624 claims with Takeda’s Cas12f “D326A mutant” that “did not cleave the target DNA” (See page 560) so as to make a target transcription inhibitor system because use of a defective Cas enzyme having no DNA cleavage/nickase activity in combination with a gRNA and KRAB for the purpose of repressing gene expression via the “CRISPRi transcription suppression technology” (see page 2 of Zhao) was widely known and practiced in the prior art as evidenced by Yamagata and Zhao.
Claims 1, 4-11, and 13-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of copending Application No. 18/290,467 in view of Takeda et al. (Molecular Cell, 2021, 81:558-570), Yamagata et al. (US 2019/0376088 A1), and Zhao et al. (Frontiers in Molecular Biosciences, 2021, 8:652392).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the ‘467 claims drawn to and require a composition comprising Cas12f1 and an engineered gRNA comprising the instantly claimed nucleotide sequences. See SEQ ID NOs:382 and 116, for instance. It would have been obvious to replace Cas2f1 of the ‘825 claims with Takeda’s Cas12f “D326A mutant” that “did not cleave the target DNA” (See page 560) so as to make a target transcription inhibitor system because use of a defective Cas enzyme having no DNA cleavage/nickase activity in combination with a gRNA and KRAB for the purpose of repressing gene expression via the “CRISPRi transcription suppression technology” (see page 2 of Zhao) was widely known and practiced in the prior art as evidenced by Yamagata and Zhao.
Claims 1, 4-11, and 13-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-43 of copending Application No. 18/576,676 in view of Takeda et al. (Molecular Cell, 2021, 81:558-570), Yamagata et al. (US 2019/0376088 A1), and Zhao et al. (Frontiers in Molecular Biosciences, 2021, 8:652392).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the ‘676 claims drawn to and require a composition comprising Cas12f1 and an engineered gRNA comprising the instantly claimed nucleotide sequences. See SEQ ID NO:67 for instance. It would have been obvious to replace Cas2f1 of the ‘676 claims with Takeda’s Cas12f “D326A mutant” that “did not cleave the target DNA” (See page 560) so as to make a target transcription inhibitor system because use of a defective Cas enzyme having no DNA cleavage/nickase activity in combination with a gRNA and KRAB for the purpose of repressing gene expression via the “CRISPRi transcription suppression technology” (see page 2 of Zhao) was widely known and practiced in the prior art as evidenced by Yamagata and Zhao.
Claims 1, 4-11, and 13-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-43, 92, and 95-99 of copending Application No. 18/837,428 in view of Takeda et al. (Molecular Cell, 2021, 81:558-570), Yamagata et al. (US 2019/0376088 A1), and Zhao et al. (Frontiers in Molecular Biosciences, 2021, 8:652392).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the ‘428 claims drawn to and require a composition comprising Cas12f1 and an engineered gRNA comprising the instantly claimed nucleotide sequences. See SEQ ID NOs:120 and 132, for instance. It would have been obvious to replace Cas2f1 of the ‘428 claims with Takeda’s Cas12f “D326A mutant” that “did not cleave the target DNA” (See page 560) so as to make a target transcription inhibitor system because use of a defective Cas enzyme having no DNA cleavage/nickase activity in combination with a gRNA and KRAB for the purpose of repressing gene expression via the “CRISPRi transcription suppression technology” (see page 2 of Zhao) was widely known and practiced in the prior art as evidenced by Yamagata and Zhao.
Claims 1, 4-11, and 13-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 131-171 of copending Application No. 18/845,108 in view of Takeda et al. (Molecular Cell, 2021, 81:558-570), Yamagata et al. (US 2019/0376088 A1), and Zhao et al. (Frontiers in Molecular Biosciences, 2021, 8:652392).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the ‘108 claims drawn to and require a composition comprising Cas12f1 and an engineered gRNA of Formula (I) comprising the instantly claimed nucleotide sequences. It would have been obvious to replace Cas2f1 of the ‘108 claims with Takeda’s Cas12f “D326A mutant” that “did not cleave the target DNA” (See page 560) so as to make a target transcription inhibitor system because use of a defective Cas enzyme having no DNA cleavage/nickase activity in combination with a gRNA and KRAB for the purpose of repressing gene expression via the “CRISPRi transcription suppression technology” (see page 2 of Zhao) was widely known and practiced in the prior art as evidenced by Yamagata and Zhao.
Claims 1, 4-11, and 13-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 10-11, 14, 17-18, 20-32, 34, 37, and 40 of copending Application No. 18/845,663 in view of Takeda et al. (Molecular Cell, 2021, 81:558-570), Yamagata et al. (US 2019/0376088 A1), and Zhao et al. (Frontiers in Molecular Biosciences, 2021, 8:652392).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the ‘428 claims drawn to and require a composition comprising Cas12f1 and an engineered gRNA comprising the instantly claimed nucleotide sequences. See SEQ ID NOs:120 and 132, for instance. It would have been obvious to replace Cas2f1 of the ‘825 claims with Takeda’s Cas12f “D326A mutant” that “did not cleave the target DNA” (See page 560) so as to make a target transcription inhibitor system because use of a defective Cas enzyme having no DNA cleavage/nickase activity in combination with a gRNA and KRAB for the purpose of repressing gene expression via the “CRISPRi transcription suppression technology” (see page 2 of Zhao) was widely known and practiced in the prior art as evidenced by Yamagata and Zhao.
Claims 1, 4-11, and 13-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16, 18-21, 43, 48-50, 52-55, and 57-59 of copending Application No. 18/853,023 in view of Takeda et al. (Molecular Cell, 2021, 81:558-570), Yamagata et al. (US 2019/0376088 A1), and Zhao et al. (Frontiers in Molecular Biosciences, 2021, 8:652392).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the ‘023 claims drawn to and require a composition comprising Cas12f1 and an engineered gRNA comprising the instantly claimed nucleotide sequences. See SEQ ID Nos:284 and 296, for instance. It would have been obvious to replace Cas2f1 of the ‘023 claims with Takeda’s Cas12f “D326A mutant” that “did not cleave the target DNA” (See page 560) so as to make a target transcription inhibitor system because use of a defective Cas enzyme having no DNA cleavage/nickase activity in combination with a gRNA and KRAB for the purpose of repressing gene expression via the “CRISPRi transcription suppression technology” (see page 2 of Zhao) was widely known and practiced in the prior art as evidenced by Yamagata and Zhao.
Claims 1, 4-11, and 13-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 and 9-20 of copending Application No. 18/853,825 in view of Takeda et al. (Molecular Cell, 2021, 81:558-570), Yamagata et al. (US 2019/0376088 A1), and Zhao et al. (Frontiers in Molecular Biosciences, 2021, 8:652392).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the ‘825 claims drawn to and require a composition comprising Cas12f1 and an engineered gRNA comprising the instantly claimed nucleotide sequences. It would have been obvious to replace Cas2f1 of the ‘825 claims with Takeda’s Cas12f “D326A mutant” that “did not cleave the target DNA” (See page 560) so as to make a target transcription inhibitor system because use of a defective Cas enzyme having no DNA cleavage/nickase activity in combination with a gRNA and KRAB for the purpose of repressing gene expression via the “CRISPRi transcription suppression technology” (see page 2 of Zhao) was widely known and practiced in the prior art as evidenced by Yamagata and Zhao.
Conclusion
No claim is allowed.
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/DANA H SHIN/Primary Examiner, Art Unit 1635
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