DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This application is a CON application of 16794137 (now abandoned), which is a CIP of 15727279 (now Patent # US 10669539), which claims priority to Provisional Application # 62/405070, filed on 10/06/2016.
Status of the Claims
Claim 1 is under examination.
Specification
35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, requires the specification to be written in “full, clear, concise, and exact terms.”. On page 7 line 30, in the description of Figures, the text states: The asterisk (*) indicates that the reaction is not strictly reversible…; However, no (*) can be found in any of the Figures.
Appropriate correction is required.
Claim Objections
Claim 1 is objected to because of the following informalities:
On line 2, the claim recites: …comprising a sequence encoding for a constant region…
Amending it to recite: comprising a sequence that encodes a constant region or comprising a sequence encoding would improve the grammar of the claim.
Appropriate correction is required.
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.
Claim 1 is 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" in “the sequence” in line 4. There is insufficient antecedent basis for this limitation in the claim because the claim in line 3 recites comprising a sequence encoding…. a constant region…the sequence comprising…. It isn’t clear if the sequence refers to the sequence that encodes the constant region or refers to a sequence outside of the coding region for the constant region.
Regarding claim 1 again, it is noted that the claim recites : “the sequence comprising a non-palindromic recognition sequence for a type II restriction endonuclease…” This language is considered to be indefinite because type II restriction endonucleases are known to have several non-palindromic recognition sequences; therefore it isn’t clear which non-palindromic recognition sequence is being referred to. It is noted that the specification bridging pgs. 8 - 9 states: FIGURE 6B shows polynucleotides of various embodiments encoding for an sgRNA or crRNA recognized by a CRIPSR Cas9 protein and having non-palindromic recognition site for MmeI, NmeAIII, HpaII or MspI, ScrFI, and BfaI. However, the claim remains indefinite because such disclosure is not a limiting definition for non-palindromic sequence.
Claim Interpretation
Claim 1 is being interpreted as:
A method for generating a DNA molecule encoding an RNA component of a CRISPR complex, the method comprising:
(a) providing a polynucleotide comprising a sequence encoding:
i. a constant region comprising a protein binding segment of an RNA component of a CRISPR complex, and
ii. a non-palindromic recognition sequence for a type II restriction endonuclease
wherein the latter cleaves at least 17 nucleotides outside of the non-palindromic recognition sequence, the non-palindromic recognition sequence being oriented such that, when bound to the type II restriction endonuclease, a DNA cleavage domain of the type II restriction endonuclease is positioned outside of the constant region;
(b) cleaving a first DNA molecule with a first restriction endonuclease
wherein a recognition sequence of the first restriction endonuclease comprises a protospacer adjacent motif recognized by the CRISPR complex,
to generate a cleaved DNA molecule;
(c) generating a covalent bond between the cleaved DNA molecule and the polynucleotide (of step (a))
to generate an intermediate DNA molecule; and
(d) cleaving the intermediate DNA molecule (of step (c)) with a second restriction endonuclease that recognizes the non-palindromic recognition sequence of the polynucleotide (as recited in (a)ii.)
to generate a final DNA molecule encoding an RNA component of the CRISPR complex.
Nothing in the specification indicates that the method is performed in one tube. The example on pg. 53 explicitly discloses dividing the digestion and ligation steps to be performed in two tubes. Therefore, the claim is further being interpreted as not requiring restriction digestion and ligation steps to be performed in one tube.
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)(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 is rejected under 35 U.S.C. 102(a)(2) as being clearly anticipated by WO2016196805A1, filed 2nd June, 2016, herein referred to as Lane and cited in IDS of 09/04/2024.
Regarding claim 1, Lane teaches a digestion/ligation method for generating a library of Cas9 single guide RNAs or Cas9 targeter RNAs) (abstract). In step (a) Lane’s method comprises: providing an adapter, the adapter comprising a sequence encoding a protein binding segment of an RNA component of a CRISPR complex (summary [0010] recitation: In some cases, the first DNA adapter includes the DNA encoding the constant region of a Cas9 sgRNA). Lane’s adapter further comprises a second recognition sequence for a second restriction enzyme (summary [0011] recitation: In some cases, the first DNA adapter includes two recognition sequences). In step (b) Lane’s method comprises: combining a target sample with a first restriction enzyme, the polynucleotide, and a first ligase; the target sample comprising a first recognition sequence for the first restriction enzyme, the first recognition sequence comprising a protospacer adjacent motif (PAM) (summary [0008] recitation: the step of cleaving a target DNA ...with one or more DNA endonucleases (PAM-recognition DNA endonucleases) that specifically bind to and cleave within a recognition sequence that includes a PAM sequence). Further, the first restriction enzyme in Lane’s method is configured to cleave the first recognition sequence to produce a cleaved fragment (summary [0008] recitation: thereby generating a plurality of DNA cleavage fragments). Lane’s method follows the restriction digestion step with a ligation step such that the first ligase is configured to operably link (summary [0008] recitation: A DNA adapter can be ligated (i.e., generating a covalent bond) to the cleaved fragment to generate an intermediate adapter. Lane further teaches combining the intermediate adapter with the second restriction enzyme (summary [0008] recitation: ...and then contacted with a distal-cleaving DNA endonuclease), and further steps ([0012] onwards). Lane teaches the use of MmeI as the second restriction enzyme ([0011] recitation: the second DNA endonuclease is selected from the group consisting of: ... MmeI). Lane’s choice of restriction digestion is configured to cleave the intermediate adapter at least 17 nucleotides outside of the second recognition sequence ([0009], and [0011] recitation: In some cases, the second DNA endonuclease cleaves at a distance of from 17 to 30 nucleotides from its recognition sequence). The recognition sequence for MmeI comprises a non-palindromic recognition sequence, see Lane’s disclosure of several non-palindromic recognition sequences for the second restriction enzyme, in [00190] recitation: In some cases, a subject distal cleaving DNA endonuclease is a type IIG DNA endonuclease (type IIG restriction enzyme).
See [00284] for Lane’s Protocol and relevant recitation below:
Step 2. Add the following (restriction enzyme) to each tube...
Step 6. Transfer to a 1.5 ml tube
Step 7. Dialyze (digested) sample against ddH20 on dialysis disc for 20 minutes to desalt and improve blunt ligation efficiency.
Step 8. For ligations, ...17 pl DNA (digest) + ligase...
Thus, Lane clearly anticipates instant claim 1.
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.
This rejection is being written preemptively for an embodiment not claimed, wherein digestion and ligation steps are to be performed in one tube.
Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over Lane (WO2016196805A1), filed 2nd June, 2016, as applied to claim 1 above, and further in view of NEB’s CutSmart Brochure NEB’s CutSmart (Product # B7204S) Brochure, Pg.6, (First Use Year: 2013), https://www.neb.com/en-us/products/b7204-cutsmart-buffer#Product%20Information), and Ampure XP BEads (Agencourt AmPure XP (Product #: Beckman A63880) Pg.4, (First Use Year: 2013), https://www.beckman.com/search#q=A63880&t=coveo-tab-techdocs; Protocol, 2016) corresponding to commercially available products and as cited in parent app 16/794137; not being cited on instant 892.
Lane does not explicitly teach combining restriction digestion and ligation in one step and in one tube.
However, at the time of the effective filing date, NEB reduced to practice a buffer compatible for use with hundreds of restriction enzymes and ligases, known as CutSmart buffer and commercially available. See Pg. 6 of CutSmart Brochure, including table titled, “Activity of DNA Modifying Enzymes in CutSmart Buffer” showing restriction digestion and ligation can be carried out simultaneously as the enzymes required for the two work in the same buffer.
Further, at the time of the effective filing date, Ampure XP beads (Product Beckman A63880) were commercially available that allowed for several reactions and clean-ups to be performed in a single tube. See Figure 1 on Pg. 16 of Ampure Protocol titled “Workflow for PCR Purification” showing how magnetic beads may be used to carry out multiple steps in a single vessel.
It would have been prima facie obvious to a person of ordinary skill in the art at the time the effective filing date to combine restriction digestion and ligation in one step and in one tube using the commercially available products as discussed above to arrive at the claimed invention. A person of ordinary skill in the art would consider a one-step/tube reaction compared with a two-step/tube reaction as functional equivalents as long as the reaction conditions remained the same. Since a one-step/tube reaction can reduce the time taken for the same reaction carried out in a two-step/tube reaction, it would be a simple substitution for one of ordinary skill in the art to use a one-step/tube reaction instead of two as in the method of Lane. See MPEP 2143 I.(B). One of ordinary skill in the art would have been motivated to combine the teaching to shorten the time needed to carry out the method of library preparation.
Therefore the invention as a whole would have been prima facie obvious to one ordinary skill in the art at the time of 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.
Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 16 of U.S. Patent No. 10669539. Although the claims at issue are not identical, they are not patentably distinct from each other because they are both drawn to a method of making an oligonucleotide that is a sgRNA as disclosed in the title and abstract of the two applications; ref app title reads: …methods, and systems for generating clustered regularly interspaced short palindromic repeats (CRISPR) Guide RNA libraries. See comparison of the independent claims of ref app with claim 1 of instant app below. While ref app claims do not explicitly recite “method” the composition recited in the reference app is the same as that used in instant method. it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to look specifically for a method to make a sgRNA, in the specification of the reference application and to have come across the title, abstract, [0016], [0017], [0162], [0167], [0174] – till end and arrive at instant method for generating an RNA component of a clustered regularly interspaced short palindromic repeats (CRISPR) complex.
10669539 Claim 1/ 12
18734879 claim 1
A polynucleotide/kit for generating CRISPR guide RNA (gRNA) libraries comprising:
(a) a sequence
i. encoding for a constant region comprising a protein binding segment of an RNA component of a CRISPR complex
ii. comprising a non-palindromic recognition sequence for a type II restriction endonuclease configured to cleave at least 17 nucleotides outside of the non-palindromic recognition sequence, the non-palindromic recognition sequence being oriented such that, when bound to the type II restriction endonuclease, a DNA cleavage domain of the type II restriction endonuclease is positioned outside of the constant region;
group inhibits activity of the second restriction enzyme;
(b) combining a polynucleotide sample with a first restriction enzyme, the first adapter, and a first ligase; the polynucleotide sample comprising a first recognition sequence for the first restriction enzyme, the first recognition sequence comprising a protospacer adjacent motif (PAM); the first restriction enzyme being configured to
i. cleave the first recognition sequence to produce a cleaved fragment;
ii. the first ligase is configured to operably linking the first adapter to the cleaved fragment to generate an intermediate polynucleotide, wherein the intermediate polynucleotide does not contain the first recognition sequence;
(c) combining the intermediate polynucleotide with the second restriction enzyme, a second adapter, and a second ligase; the second ligase is configured to operably linking the methylated polynucleotide to the second adapter to generate a final polynucleotide.
A method for generating a DNA molecule encoding an RNA component of a CRISPR complex, the method comprising:
(a) providing a polynucleotide comprising
i. a sequence encoding for a constant region comprising a protein binding segment of an RNA component of a CRISPR complex,
ii. the sequence comprising a non-palindromic recognition sequence for a type II restriction endonuclease configured to cleave at least 17 nucleotides outside of the non-palindromic recognition sequence, the non-palindromic recognition sequence being oriented such that, when bound to the type II restriction endonuclease, a DNA cleavage domain of the type II restriction endonuclease is positioned outside of the constant region;
(b) i. cleaving a first DNA molecule with a first restriction endonuclease wherein a recognition sequence of the first restriction endonuclease comprises a protospacer adjacent motif recognized by the CRISPR complex, to generate a cleaved DNA molecule;
ii. generating a covalent bond between the cleaved DNA molecule and the polynucleotide to generate an intermediate DNA molecule; and
(c) cleaving the intermediate DNA molecule with a second restriction endonuclease that recognizes the non-palindromic recognition sequence of the polynucleotide
to generate a final DNA molecule encoding an RNA component of the CRISPR complex.
Any additional limitations of the ‘539 claims are encompassed by the open claim language “comprises” found in the instant claims.
Conclusion
No claims are allowable.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHABANA MEYERING, Ph.D. whose telephone number is (703)756-4603. The examiner can normally be reached M - F: 9am to 5pm EST.
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/SHABANA S MEYERING/Examiner, Art Unit 1635
/SHABANA S MEYERING/Examiner, Art Unit 1635
/RAM R SHUKLA/Supervisory Patent Examiner, Art Unit 1635