DETAILED CORRESPONDENCE
Application Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Claims 1-20 and 25 are pending.
Priority
3. Acknowledgement is made of applicants’ claimed domestic priority to U.S. Provisional Application No. 63/155103, filed on 03/01/2021.
Information Disclosure Statement
4. The IDS filed on 10/04/2023 has been considered by the examiner and a copy of the Form PTO/SB/08 is attached to the office action.
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 and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). See p. 31-35, p. 39, and Tables 1 and 3.
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 sequence identifiers, 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.
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings 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. See Figures 4 and 9.
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.
Duplicate Claim Warning
5. Applicant is advised that should claim 16 be found allowable, claim 17 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. 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(b)
6. 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.
7. Claims 10-15, 18-19, and 25 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.
The term "about" in claims 10-15 and 18-19 is a relative term which renders the claim indefinite. The term "about" is a term of degree and the examiner has reviewed the specification and can find no examples or teachings that can be used for ascertaining the variance intended by the recited term of degree. Moreover, there is nothing in the specification or prior art of record to indicate that one of ordinary skill in the art could have ascertain the scope of the recited degree. It is suggested that applicant clarify the meaning of the claims. See Supplementary Examination Guidelines for Determining Compliance with 35 U.S.C. §112 and for Treatment of Related Issues in Patent Applications, 76 FR 7162 (Feb. 9, 2011), page 7165.
Regarding claim 25, there is insufficient antecedent basis for the limitation “the bride oligonucleotide”. It is suggested that applicants clarify the meaning of the claims.
Claim Rejections - 35 USC § 102
8. 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.
9. Claims 1-17, 20 and 25 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gersbach et al. (US Patent Application Publication 2020/0347105 A1, published on 11/5/2020 with priority to 06/11/2018; examiner cited).
10. Claims 1-17, 20 and 25 are drawn to a method of generating a CRISPR array, the method comprising: providing a first oligonucleotide comprising a CRISPR repeat sequence or a portion thereof, and a first portion of a first space sequence at its 3’end; providing a second oligonucleotide comprising, from 5’ to 3’, a second portion of the first spacer sequence, the CRISPR repeat sequence, and a first portion of a second spacer sequence; providing a bridge oligonucleotide comprising a sequence substantially complementary to the first spacer sequence; allowing the first oligonucleotide and the second oligonucleotide to hybridize with the bridge oligonucleotide; and ligating the first and second oligonucleotide.
11. With respect to claim 1, Gersbach et al. teach a method of generating a CRISPR array comprising providing a first oligonucleotide comprising CRISPR repeat sequence or a portion thereof, and a first portion of a first spacer sequence at its 3’ end; providing a second oligonucleotide comprising from 5’ to 3’, a second portion of the first spacer sequence, the CRISPR repeat sequence, and first portion of a second spacer sequence; providing a protospacer sequence (bridge oligonucleotide) comprising a sequence substantially complementary to the first spacer sequence; allowing the first oligonucleotide and the second oligonucleotide to hybridize with the protospacer sequence and ligating the first and second oligonucleotide [see Abstract; paragraphs 0007; 0024; 0059; 0075; 0111-0112; 0174-0175].
With respect to claim 2, Gersbach et al. teach the method wherein the first oligonucleotide further comprises a flanking sequence at its 5’ end [see paragraph 0194].
With respect to claim 3, Gersbach et al. teach a method of generating a CRISPR array comprising providing a first oligonucleotide comprising CRISPR repeat sequence or a portion thereof, and a first portion of a first spacer sequence at its 3’ end; providing a second oligonucleotide comprising from 5’ to 3’, a second portion of the first spacer sequence, the CRISPR repeat sequence, and first portion of a second spacer sequence; providing a protospacer sequence (bridge oligonucleotide) comprising a sequence substantially complementary to the first spacer sequence; allowing the first oligonucleotide and the second oligonucleotide to hybridize with the protospacer sequence and ligating the first and second oligonucleotide [see Abstract; paragraphs 0007; 0024; 0059; 0075; 0111-0112; 0174-0175].
With respect to claim 4, Gersbach et al. teach the method wherein the flanking sequence comprises a portion of a sequence of a vector [see paragraph 0209].
With respect to claim 5, Gersbach et al. teach the method wherein the first oligonucleotide further comprises at its 5’ end, a portion of a third spacer sequence [see paragraphs 0016, 0024, 0075, 0116, 0199].
With respect to claim 6, Gersbach et al. teach the method wherein the first oligonucleotide comprises a third spacer sequence, a CRISPR repeat sequence or a portion thereof, and a first portion of a first spacer sequence at its 3’ end [see paragraphs 0007, 0016, 0024, 0059, 0075, 0111-0112, 0116, 0174-0175, 0199].
With respect to claim 7, Gersbach et al. teach wherein the protospacer sequence (bridge oligonucleotide) comprising a sequence substantially complementary to a portion of the CRISPR repeat sequence at its 5’ or 3’ end [see paragraphs 0187-0189].
With respect to claim 8, Gersbach et al. teach the method wherein the portion of the CRISPR repeat sequence comprises about 1 to about 10 nucleotides [see paragraph 0177].
With respect to claim 9, Gersbach et al. teach the method wherein the protospacer sequence (bridge oligonucleotide) comprises from 5’ to 3’ a sequence substantially to a first portion of the CRISPR repeat sequence, the sequence substantially complementary to the first spacer sequence, and a sequence substantially complementary to a second portion of the CRISPR repeat sequence [see paragraphs 0007; 0024; 0059; 0075; 0111-0112; 0174-0175; 0187-0189].
With respect to claim 10, Gersbach et al. teach the method wherein the first and/or second portion of the repeat sequence comprises about 1 to about 10 nucleotides [see paragraph 0177].
With respect to claims 11 and 12, Gerbsach et al. teach the method wherein each of the first and second oligonucleotides comprises about 40 or more nucleotides (encompasses the claimed range as “or more” can be interpreted as any value over 40 nucleotides) [see paragraph 0177]
With respect to claim 13, Gersbach et al. teach the method wherein the CRISPR repeat sequence comprises about 15 to 36 nucleotides [see paragraph 0177].
With respect to claim 14, Gersbach et al. teach the method wherein the protospacer sequence comprises about 30 to 50 nucleotides [see paragraph 0116].
With respect to claim 15, Gersbach et al. teach the method wherein teach of the first portion of the first spacer sequence, the second portion of the first spacer sequence, and the first portion of the second spacer sequence comprising about 5 to about 20 nucleotides [see paragraph 0116].
With respect to claims 16 and 17, Gersbach et al. teach the method wherein the first spacer sequence comprises a first target site in a target gene, and the second spacer sequence comprises a second target site in the target gene [see paragraphs 0009-0013; 0116].
With respect to claim 20, Gersbach et al. teach the method wherein the first oligonucleotide, the second oligonucleotide and the bridge oligonucleotide are DNA oligonucleotides [see paragraph 0084].
With respect to claim 25, Gersbach et al. teach the method further comprising generating a strand complementary to the ligated first and second oligonucleotide, wherein the complementary strand comprises the bridge oligonucleotide, thereby generating a double-strand construct [see paragraphs 0007; 0024; 0059; 0075; 0100; 0111-0112; 0174-0175; 0187-0189].
Claim Rejections - 35 USC § 103
12. 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.
13. Claim(s) 18 and 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gersbach et al. (US Patent Application Publication 2020/0347105 A1, published on 11/5/2020 with priority to 06/11/2018; examiner cited).
14. The relevant teachings of Gersbach et al. as applied to claims 1-17, 20 and 25 are set forth in the 102 rejection above.
With respect to claims 18 and 19, Gersbach et al. teach a method of generating a CRISPR array comprising providing a first oligonucleotide comprising CRISPR repeat sequence or a portion thereof, and a first portion of a first spacer sequence at its 3’ end; providing a second oligonucleotide comprising from 5’ to 3’, a second portion of the first spacer sequence, the CRISPR repeat sequence, and first portion of a second spacer sequence; providing a protospacer sequence (bridge oligonucleotide) comprising a sequence substantially complementary to the first spacer sequence; allowing the first oligonucleotide and the second oligonucleotide to hybridize with the protospacer sequence and ligating the first and second oligonucleotide [see Abstract; paragraphs 0007; 0024; 0059; 0075; 0111-0112; 0174-0175].
Although Gersbach et al. does not specifically teach the method of claims 18 and 19 wherein the bridge oligonucleotide is used at a ratio of between about 2:1 and about 3:1 by molarity in relation to a mixture of the first and second oligonucleotides and wherein the amount of the first and second oligonucleotides in the mixture are about equal, MPEP 2144.05.II.A states “[g]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)”. In the instant case, it would have been obvious for one of ordinary skill in the art creating the CRISPR array of Gersbach et al. to optimize the ratios of oligonucleotides in order to maximize the efficiency and effectiveness of the array production. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
15. Status of the claims:
Claims 1-20 and 25 are pending.
Claims 1-20 and 25 are rejected.
No claims are in condition for an allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PAUL J HOLLAND whose telephone number is (571)270-3537. The examiner can normally be reached Monday to Friday from 8AM to 5PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached at 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/PAUL J HOLLAND/Primary Examiner, Art Unit 1656