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 .
Claims 1-10 and 19-23 are pending in the application.
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 2, 21-23 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.
Regarding claim 2, the use of trade name “TALEN” renders the claim indefinite because this term is used in the claim as a limitation to identify a particular material (Ex parte Simpson, 218 USPQ 1020). The use of a trademark or trade name in a claim to identify or describe a material or product would not only render a claim indefinite, but would also constitute an improper use of trademark or trade name (see MPEP 2173.05 (u)).
Regarding claim 21, the recitation of “wherein the fusion protein comprises at least one endonuclease CRISPR protein, a DNA binding moiety that is a zinc finger protein” renders the claim infinite because it is unclear whether it means the fusion protein comprises, CRISPR protein, DNA binding moiety, or both.
Regarding claim 22 and 23, the recitation of “the kit of claim 21, further comprising a fluorescent labeled protein, or nuclear localization signal” renders the claims indefinite because it is unclear where the fluorescent protein and nuclear localization signal is located. Is it on the vector encoding fusion protein, the template, or separate from both?
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 2, 4, 6, 9, 10, 19, 21, 22 and 23 is/are rejected under 35 U.S.C. 102(a1)(a2) as being anticipated by Gregory (US 8,313,925, IDS).
Regarding claims 1, 2 and 4, Gregory teaches a vector encoding a fusion protein comprising FokI cleavage domain and a Zinc Finger Domain (Figure 8, and col.6, lines 54-55).
Regarding claim 6, Gregory teaches said fusion protein comprises a linker extends from residues 134-143, which is 9 amino acids, that joins ZFP and FokI (col.8, lines 39-44).
Regarding claims 9 and 10, Gregory teaches the fusion protein comprises a nuclear localization signal, which is from SV40 NLS (col.89, line 48-50).
Regarding claims 19 and 21, Gregory teaches the vector that encoding a fusion protein comprising ZFN fusion that has a zinc finger binding domain and FokI nuclease (Figure 8, and col.6, lines 54-55), and a donor sequence, which may be a template, wherein the donor sequence comprises exogenous sequences and flanked by homologous sequences, wherein the exemplary exogenous sequences include promoter sequences, enhancer sequences, epitope tags, marker genes, cleavage enzyme recognition sites and various types of expression cassettes (col.53, lines 42-52, 53-56). The donor sequence that comprises a promoter and/or enhancer is necessarily a “DNA binding moiety sequence” because transcription factors and/or enhancer proteins bind to such sequence to regulate expression the encoded protein in the expression cassette.
Regarding claim 22, Gregory teaches the marker genes within the exogenous sequence may be green fluorescent protein, which is a fluorescent labeled protein (col.53, line 61).
Regarding claim 23, Gregory teaches nuclear localization signal (NLS) (Figure 8, and col.6, lines 54-55).
Claim(s) 1, 2, 4, 5, 6, 9, 19, 21 and 23 is/are rejected under 35 U.S.C. 102 (a1)(a2) as being anticipated by Cost (US 2013/0326645, IDS).
Cost teaches a vector that encodes a fusion protein that comprises a zinc finger domain (DNA binding moiety) and an endonuclease domain, FokI (paragraph [0237] and [0348]). Therefore, the teaching from Cost anticipates the claimed invention of claims 1, 2, 4.
Regarding claim 5, Cost teaches the zinc finger targets CCR5 ([0008], [0021], [0024] and [0197]; Figure 8B).
Regarding claim 6 and 9, Cost teaches the zinc finger domain is joined to FokI domain by 4 amino acid linker and also includes NLS (paragraph [0237] and [0348]).
Regarding claims 19, 21 and 23, Cost teaches vector encoding the fusion protein and donor sequences/template sequences comprising a transgene expression cassette comprising a promoter and a coding sequence, two flanking sequences and two flanking sites bound by the fusion protein (paragraph [0008]-[0010], [0017], [0062] and [0141], Figure 1, [0348]).
Claim(s) 1-3, 9, 10 is/are rejected under 35 U.S.C. 102(a1)(a2) as being anticipated by Doudna (2014/0068797, IDS).
Regarding claims 1-3, Doudna teaches a vector encoding a fusion protein comprising at least one endonuclease and a DNA binding moiety, a fusion protein comprising Cas9 and transcription factors (paragraph [0216], [0241], [0456], bottom lines, [0419] and Figure 54). The teaching from Doudna anticipates the claimed invention of claims 1-3 because Cas9 has nuclease activity and the transcription factor meets the limitation of a DNA binding moiety.
Regarding claims 9 and 10, Doudna teaches the Cas9 is fused with NLS, and the NLS is from SV40 (paragraph [241], [0456], and [0736]).
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.
Claim(s) 7 and 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gregory, in view of Doudna.
The teaching from Gregory has been discussed above.
However, Gregory does not teach the fusion protein further comprises a fluorescent labeled protein such as GFP.
Doudna teaches fusion protein that comprises Cas9 nuclease and fluorescent labeled protein such as GFP (paragraph [0241], [0456]), which is used for tracking the expression of the Cas9 protein.
It would have been obvious to an ordinary skilled in the art to modify the fusion protein taught by Gregory to further include a fluorescent labeled protein such as GFP based on combined teaching from Gregory and Doudna. The ordinary skilled in the art would have been motivated to make such a modification to receive the expected benefit of providing a fusion protein that is easily tracked as taught by Doudna. The ordinary skilled in the art would have reasonable expectation of success to link the GFP to the fusion protein taught by Gregory following combined teaching from Gregory and Doudna. Therefore, the claimed invention of claims 7 and 8 would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
Claim(s) 19-23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Doudna (IDS), in view of Mali (IDS).
The teaching from Doudna has been discussed above.
Doudna also teach a donor polynucleotide (template) of various length that comprises homologous flanking sequences for integrating the sequence into genomic DNA (paragraph [0299] and [00300]). Doudna teaches the donor sequences may comprise selectable markers such as drug resistance genes, fluorescent proteins, enzymes (paragraph [0302]) and be provided to the cell as single stranded DNA or double stranded DNA in linear or circular form (paragraph [0302]).
However, Doudna does not teach the donor polynucleotide (template) comprises an expression cassette.
Mali teaches the use of homologous recombination using hCas9 and gRNA to integrate a double stranded donor construct into a native AAVS1 locus human cells, wherein the donor construct comprises an expression cassette encoding a puromycin selection marker (page 824, right col., full paragraph, and Figs. 2A and C-F). Mali teaches that puromycin selection readily derived cells modified to integrate the expression cassette (page 824, right col., full paragraph, and Figs. 2A and C-F).
It would have been obvious to an ordinary skilled in the art that expression cassette encoding puromycin taught by Mali may be used as donor polynucleotide in the system of integrating donor polynucleotide taught by Doudna because Doudna teaches integrating selection marker (paragraph [0302]). The ordinary skilled in the art would be motivated to combine the fusion protein taught by Doudna and donor polynucleotide comprising the expression cassette to express the selectable marker at desired location within the genome as demonstrated by Mali. The promoter within the expression cassette meets the limitation of a DNA binding moiety sequence because it binds transcription factors. Therefore, the claimed invention of claims 19 and 21 would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
Regarding claim 20, Doudna teaches gRNAs for directing Cas9 to the desired cleavage site.
Regarding claim 22 and 23, Doudna teaches the Cas9 fusion to a fluorescent labeled protein, or a NLS (paragraph [0456]).
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CELINE X QIAN whose telephone number is (571)272-0777. The examiner can normally be reached M-F (8-4:00).
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/CELINE X QIAN/ Primary Examiner, Art Unit 1637