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 .
Applicants’ filed a Preliminary Amendment on December 13, 2022, in which they canceled claims 1-49 and added new claims 50-68. Thus, claims 50-68 are pending in this application and are under examination.
Information Disclosure Statement
The Information Disclosure Statements filed December 13, 2022 and April 13, 2023 have been considered.
Drawings
The drawings are objected to because the drawings should be labeled “FIG. 1,” “FIG. 2,” etc., and if more than one panel is present in a drawing, capital letters should be noted for each panel. For example, “Figure 1.” Should be changed to “FIGS. 1A-1C.” 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.
Specification
The disclosure is objected to because of the following informalities:
The Incorporation by Reference paragraph at page 47 should be deleted.
The use of the terms RNEASY® at page 25, line 29; MINELUTE® at page 25, line 30; GENEJET® at page 26, line 1; page 30, line 4; and page 31, line 18 ; FASTDIGEST® at page 30, line 32; and TURBOFECT® at page 33, line 6; 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 they appear 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.
Appropriate correction is required.
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 50-61 and 62-67 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 9-14, 16, 19-21, and 23 of U.S. Patent No. 9,637,739.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘739 patent and the instant application claim methods for site-specific modification of a target DNA molecule using CRISPR-Cas9 systems.
Regarding claims 50, 57, and 63, the ‘739 patent claims a method for site-specific modification of a target DNA molecule, the method comprising: preparing a polynucleotide encoding a tracrRNA and an engineered crRNA, wherein the engineered crRNA has a spacer sequence complementary to a nucleotide sequence of the DNA molecule, and wherein the polynucleotide does not encode a Cas9 protein; expressing the polynucleotide to form the tracrRNA and the engineered crRNA; and combining the tracrRNA and the engineered crRNA with a Cas9 protein to form a Cas9-crRNA complex; wherein the Cas9-crRNA complex is reprogrammed to cleave the DNA molecule (claim 1). The ‘739 patent claims that the Cas9 protein can be produced by expressing a polynucleotide encoding the Cas9 protein (claims 17-19). Regarding claims 51 and 67, the ‘739 patent claims that the polynucleotide encoding the tracrRNA and the engineered crRNA is prepared by chemical synthesis or in-vitro transcription (claim 16). Regarding claims 52 and 66, the ‘739 patent claims that the spacer sequence of the engineered crRNA comprises at least 20 nucleotides (claims 3-4). Regarding claims 53, the ‘739 patent claims the Cas9 protein comprises a mutation in a RuvC active site motif or a HNH active site motif of the Cas9 protein (claim 5).
Regarding claim 54, the ‘739 patent claims that the DNA molecule is a plasmid DNA (claims 19-21). Regarding claims 55, 58, and 64, the ‘739 patent claims contacting the Cas9-crRNA complex with the DNA molecule to cleave the DNA molecule (claim 1) Regarding claim 56, the ‘739 patent claims that the DNA molecule is double stranded (claim 10).
Regarding claims 59, the ‘739 patent claims that the DNA molecule is double stranded, and wherein the Cas9-crRNA complex modifies the DNA molecule by site-specific double stranded cleavage of the DNA molecule (claims 9-10).
Regarding claims 60 and 65, the ‘739 patent claims that the DNA molecule includes a protospacer-adjacent motif (claim 7). Regarding claim 61, the ‘739 patent claims that the Cas9 protein is a nickase (claim 14).
Therefore, the claims are not deemed to be patentably distinct.
Claims 50-53, 55, 57-58, 61-64, and 67-68 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5-8, 10, 12-14, and 17-19 of U.S. Patent No. 10,844,378.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘378 patent and the instant application claim methods for site-specific modification of a target DNA molecule using CRISPR-Cas9 systems.
Regarding claims 50, 57, and 63, the ‘378 patent claims a method for preparing a Cas9-crRNA complex that can induce site-specific modification of a target DNA molecule, the method comprising: preparing a polynucleotide encoding a tracrRNA and an engineered crRNA, wherein the engineered crRNA has a spacer sequence complementary to a nucleotide sequence of the DNA molecule, and wherein the polynucleotide does not encode a Cas9 protein; expressing the polynucleotide to form the tracrRNA and the engineered crRNA; and combining the tracrRNA and the engineered crRNA with a Cas9 protein to form a Cas9-crRNA complex; wherein the Cas9-crRNA complex is reprogrammed to cleave the DNA molecule. The ‘378 patent claims that the Cas9 protein can be produced by expressing a polynucleotide encoding the Cas9 protein (claims 1, 8, 14, and 17).
Regarding claims 51 and 67, the ‘378 patent claims that the polynucleotide encoding the tracrRNA and the engineered crRNA is prepared by chemical synthesis or in-vitro transcription (claims 2, 5, and 10). Regarding claims 52 and 66, the ‘378 patent claims that the spacer sequence of the engineered crRNA comprises at least 20 nucleotides (claims 5 and 12). Regarding claims 53, the ‘378 patent claims the Cas9 protein comprises a mutation in a RuvC active site motif or a HNH active site motif of the Cas9 protein (claims 7 and 18).
Regarding claims 55, 58, and 64, the ‘378 patent claims contacting the Cas9-crRNA complex with the DNA molecule to cleave the DNA molecule (claims 1, 8, 14, and 17) Regarding claim 61, the ‘378 patent claims that the Cas9 protein is a nickase (claim 18).
Regarding claims 62 and 68, the ‘378 patent claims that the Cas9-crRNA complex is formed in the absence of RNaseIII (claims 6, 13, and 19).
Therefore, the claims are not deemed to be patentably distinct.
Claims 50-68 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,555,187.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘187 patent and the instant application claim methods for site-specific modification of a target DNA molecule using CRISPR-Cas9 systems.
Regarding claims 50, 57, and 63, the ‘187 patent claims a method for site-specific modification of a target DNA molecule, the method comprising: preparing a polynucleotide encoding a tracrRNA and an engineered crRNA, wherein the engineered crRNA has a spacer sequence complementary to a nucleotide sequence of the DNA molecule, and wherein the polynucleotide does not encode a Cas9 protein; expressing the polynucleotide to form the tracrRNA and the engineered crRNA; and combining the tracrRNA and the engineered crRNA with a Cas9 protein to form a Cas9-crRNA complex; wherein the Cas9-crRNA complex is reprogrammed to cleave the DNA molecule (claims 1, 6, 11, and 16). The ‘187 patent claims that the Cas9 protein can be produced by expressing a polynucleotide encoding the Cas9 protein (claim 2). Regarding claims 51 and 67, the ‘187 patent claims that the polynucleotide encoding the tracrRNA and the engineered crRNA is prepared by chemical synthesis or in-vitro transcription (claims 3 and 19). Regarding claims 52 and 66, the ‘187 patent claims that the spacer sequence of the engineered crRNA comprises at least 20 nucleotides (claims 4, 14, and 18). Regarding claims 53, the ‘187 patent claims the Cas9 protein comprises a mutation in a RuvC active site motif or a HNH active site motif of the Cas9 protein (claim 5).
Regarding claim 54, the ‘187 patent claims that the DNA molecule is a plasmid DNA (claim 7). Regarding claims 55, 58, and 64, the ‘187 patent claims contacting the Cas9-crRNA complex with the DNA molecule to cleave the DNA molecule (claims 6, 11, and 16) Regarding claim 56, the ‘187 patent claims that the DNA molecule is double stranded (claim 8).
Regarding claims 59, the ‘187 patent claims that the DNA molecule is double stranded, and wherein the Cas9-crRNA complex modifies the DNA molecule by site-specific double stranded cleavage of the DNA molecule (claim 12).
Regarding claims 60 and 65, the ‘187 patent claims that the DNA molecule includes a protospacer-adjacent motif (claims 13 and 17). Regarding claim 61, the ‘187 patent claims that the Cas9 protein is a nickase (claim 15).
Regarding claims 62 and 68, the ‘187 patent claims that the Cas9-crRNA complex is formed in the absence of RNaseIII (claims 10 and 20).
Therefore, the claims are not deemed to be patentably distinct.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Jinek et al. (337 Science 816-821 (2012), and cited in the Information Disclosure Statement filed December 13, 2022) disclose cleavage of target DNA molecules in vitro using Cas9, a crRNA, and a tracrRNA, to form a complex, which is then contacted with a target DNA molecule in order for cleavage to occur (abstract, page 817 and Figure 2). Jinek discloses that the polynucleotides encoding the Cas9, crRNA, and tracrRNA are programmable, which is interpreted as including reprogramming (abstract). Jinek discloses cleavage of double-stranded plasmids using a Cas9-crRNA-tracrRNA complex (page 816, column 3, page 817, columns 1-3, and Figure 2). Jinek discloses that crRNA includes a spacer sequence flanked by identical repeats (page 816, paragraph bridging columns 1 and 2).
However, contrary to the instantly claimed invention, Jinek does not disclose that the tracrRNA and crRNA are produced by chemical synthesis or in vitro transcription. Jinek does not disclose that the Cas9-crRNA complex is formed in the absence of RNaseIII. Jinek fails to disclose or suggest that the polynucleotides encoding the Cas9 is translated to the protein Cas9 molecule during an in vitro reaction.
Sapranauskus et al. (39(21) Nucleic Acids Research 9275-9282; Supplementary Materials and Methods (August 3, 2011), and cited in the Information Disclosure Statement filed December 13, 2022) disclose that CRISPR/Cas9 provides resistance against phages and plasmids in bacteria and archaea (abstract). Sapranauskas discloses that the CRISPR/Cas9 system comprises the Cas9 enzyme and the crRNA (generated from the spacers), which guides the enzyme to interfere with invasive DNA (page 9275, column 2). Sapranauskus discloses that the CRISPR/Cas system is able to cleave plasmid and bacteriophage double-stranded DNA (page 9280, column 2). Sapranauskus discloses spacers of over 20 nucleotides (Figure 2).
However, contrary to the instantly claimed invention, Sapranauskus fails to disclose or suggest that the tracrRNA is synthetic or in-vitro transcribed.
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
Prosecution Insights