DETAILED CORRESPONDENCE
Application Status
1. The present application is being examined under the pre-AIA first to invent provisions.
2. Applicant’s amendment to the claims filed after final are acknowledged and entered into the record.
3. Claims 1, 16-21, and 30-41 are pending and examined on the merits.
4. Applicant’s remarks filed on 12/27/2019 in response to the Final Rejection mailed on 08/16/2019 are have been fully considered and are deemed persuasive to overcome the rejections and/or objections as previously applied.
The text of those sections of Title 35 U.S. Code not included in the instant action can be found in the prior Office Actions.
Withdrawn Claim Objections
5. The objection to claim 40 is withdrawn in view of applicant’s amendment to the claims to recite a sequence identifier.
Withdrawn Double Patenting
6. The terminal disclaimers filed on 12/16/2019 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of U.S. Non-provisional Application Nos. 15/230025, 14/738398, and 14/704,551 have been reviewed and is accepted. The terminal disclaimer has been recorded.
7. The provisional non-statutory double patenting rejections of claims 1, 16-21, 30-39, and 41 over the claims of copending application no. 15/230,025, 14/738398, and 14/704551 are withdrawn in view of applicant’s filing of electronic terminal disclaimers on 12/16/2019.
Claim Rejections - 35 USC § 103
8. The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
9. Claims 1, 16-21, 30-32, and 34-39 are newly rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Doudna et al. (US Patent Application Publication 2014/0068797, published on 03/06/2014 with priority to 61/652,086, filed on 05/25/2012; cited on IDS filed 02/02/2017) in view of GenBank CCK7413.1 (GenBank 09/07/2012; examiner cited). This new grounds of rejection is necessitated upon further consideration of the claims and prior art.
10. With respect to claim 1, Doudna et al. teach vectors comprising polynucleotides encoding a CRISPR enzyme, guide sequence, tracr mate sequence, and tracr sequence for interfering with a target DNA sequence in both prokaryotic and eukaryotic cells using CRISPR RNA (crRNA) and a CRISPR-associated (cas) protein/nucleic acid, operably linked to a promoter such as an inducible promoter (regulatory element) wherein the vector comprises (i) a nucleotide sequence encoding a DNA-targeting RNA, wherein the DNA-targeting RNA comprises: (a) a first segment comprising a nucleotide sequence that is complementary to a sequence in a target DNA (guide sequence) and (b) a second segment that interacts with a site-directed modifying polypeptide; and (ii) a nucleotide sequence encoding the site-directed modifying polypeptide comprising: (a) a RNA-binding portion that interacts with the DNA-targeting RNA; and (b) an activity portion that exhibits site-directed enzymatic activity, wherein the site of enzymatic activity is determined by the DNA-targeting RNA. An exemplary two-i.e., expression of those genes will be decreased) [see paragraphs 0765-0771]. Doudna et al. teach wherein when transcribed, the tracr mate sequence hybridizes to the tracr sequence and the guide sequence directs sequence specific binding of a CRISPR complex to the target sequence, and wherein the CRISPR complex comprises the CRISPR Streptococcus, Neisseria, Campylobacter, Treponema, Eubacterium, Lactobacillus, Mycoplasma, Bacteroides, Flavobacterium, Gluconacetobacter, Sutterella and Parvibaculum [see Abstract; Figures 4, 5, 6, 7, 32, 33]. Doudna et al. teach the composition wherein the Cas9 ortholog is Staphylococcus pseudintermedius [see Figure 33].
With respect to claim 16, Doudna et al. teach the composition wherein the Cas9 enzyme is a nuclease that cleaves a target DNA at a target sequence and Doudna et al. further teach the composition wherein the Cas9 is modified by mutation in the catalytic active site to catalyze nickase directed cleavage [see paragraphs 0255 and 0262].
With respect to claim 17, Doudna et al. teach the composition wherein the target DNA sequence has a length of at least 15 nucleotides [see paragraph 0166].
With respect to claim 18, Doudna et al. teach the composition wherein the CRISPR enzyme is codon-optimized for expression in a eukaryotic cell [see paragraphs 0265, 0287-0288].
With respect to claims 19-20, Doudna et al. teach the composition wherein the Cas9/Csn1 protein is mutated to reduce the naturally-occurring nuclease activity of the Cas9/Csn1 protein [see paragraph 0237], wherein in some embodiments the mutation is D10A and H840A [see paragraph 0238].
With respect to claim 21, Doudna et al. teach the composition wherein the subject chimeric site-directed modifying polypeptide comprises an activity portion that exhibits site-
With respect to claim 30, Doudna et al. teach Cas9 orthologs from Streptococcus, Neisseria, Campylobacter, Treponema, Eubacterium, Lactobacillus, Mycoplasma, Bacteroides, Flavobacterium, Gluconacetobacter, Sutterella and Parvibaculum [see Abstract; Figures 4, 5, 6, 7, 32, 33] wherein the Cas9 protein is a modified form that comprises an amino acid change such as a deletion (truncation) [see paragraph 0237] and depicts a CRISPR Cas9 enzyme comprising 500-2000 amino acids [see Figure 3]. Doudna et al. teach the composition wherein the Cas9 enzyme is a nuclease that cleaves a target DNA at a target sequence and Doudna et al. further teach the composition wherein the Cas9 is modified by mutation in the catalytic active site to catalyze nickase directed cleavage [see paragraphs 0255 and 0262]. Doudna et al. teach the composition wherein the CRISPR enzyme is codon-optimized for expression in a eukaryotic cell [see paragraphs 0265, 0287-0288]. Doudna et al. teach the composition wherein the Cas9/Csn1 protein is mutated to reduce the naturally-occurring nuclease activity of the Cas9/Csn1 protein [see paragraph 0237], wherein in some embodiments the mutation is D10A and H840A [see paragraph 0238]. Doudna et al. teach the composition wherein the subject chimeric site-directed modifying polypeptide comprises an activity portion that exhibits site-directed enzymatic activity (e.g. activity for DNA methylation, activity for DNA cleavage, activity for histone acetylation, activity for histone methylation) (interpreted as a functional domain) [see paragraph 0232]. Doudna et al. teach the composition wherein the Cas9 ortholog is Staphylococcus pseudintermedius [see Figure 33].
With respect to claim 32, Doudna et al. teach the composition wherein the vector is an adenovirus associated vector [see paragraph 0302].
With respect to claim 34, Doudna et al. teach the composition wherein the Cas9 comprises at least two nuclear localization sequences [see paragraph 0775].
With respect to claim 35, Doudna et al. teach the composition wherein the vector comprises a U6 promoter [see paragraphs 0691 and 0775].
With respect to claim 36, Doudna et al. teach the composition wherein the tracr sequence comprises at least 40 nucleotides in length [see Figure 9].
With respect to claim 37, Doudna et al. teach the composition wherein the tracr sequence comprises at least 50 nucleotides in length [see Figure 9].
With respect to claim 38, Doudna et al. teach the composition wherein the guide sequence comprises 20 nucleotides [see Figure 40].
With respect to claim 39, Doudna et al. teach the composition wherein the guide sequence comprises 20 nucleotides [see Figure 40].
Although Doudna et al. does not teach the composition wherein the Cas9 is a Staphylococcus aureus Cas9, at the time the invention was made the Cas9 protein from Staphylococcus aureus was identified and published in GenBank as accession no. CCK74173.1 [see p. 1 of GenBank referenc]. Accordingly, at the time the invention was made, it would have been obvious for one of ordinary skill in the art to combine the teachings of Doudna et al. and GenBank to utilize S. aureus Cas9 in the compositions of Doudna et al. because Doudna et al. S. aureus. One of ordinary skill in the art with the techniques of Doudna et al. in hand could readily identify through sequence alignments and with a reasonable expectation of success use the S. aureus of GenBank in the compositions of Doudna et al. because GenBank identifies the S. aureus sequence as a Cas9 ortholog. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made.
11. Claim 33 is newly rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Doudna et al. (US Patent Application Publication 2014/0068797, published on 03/06/2014 with priority to 61/652,086, filed on 05/25/2012; cited on IDS filed 02/02/2017) in view of GenBank CCK7413.1 (GenBank 09/07/2012; examiner cited) as applied to claims 1, 16-21, 30-32 and 34-39 and further in view of Xiao et al. (Journal of Virology, 1999; examiner cited).
12. The relevant teachings of Doudna et al. and GenBank as applied to claims 1, 16-21, 30-32, and 34-39 are set forth above.
With respect to claim 33, Doudna et al. teach the composition wherein the vector is an adenovirus associated vector [see paragraph 0302].
However, Doudna et al. and GenBank do not teach the composition of claim 33, wherein the vector is an AAV1, AAV2, AAV4, AAV5, or AAV8 vector.
Xiao et al. teach that AAV vectors are promising for human gene therapy. Xiao et al. further teach that AAV-1 serotype may be preferred in some applications of human gene therapy, and that AAV expression will persist for a prolonged period of time in most target
At the time the invention was made, it would have been obvious for one of ordinary skill in the art to combine the teachings of Doudna et al., GenBank, and Xiao et al. to use an AAV serotype such as AAV-1 because Doudna et al. and GenBank teach compositions for targeted gene therapy comprising AAV vectors. Xiao et al. teach that AAV-1 may be preferred in some applications of human gene therapy, and use of vectors based on different serotypes would allow for at least two treatments. One of ordinary skill in the art would have had a reasonable expectation of success and a reasonable level of predictability to combine the teachings of Doudna et al., GenBank, and Xiao et al. because Xiao et al. acknowledges that the use of AAV vectors based on different serotypes would allow for multiple treatements. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Conclusion
13. Status of the claims:
Claims 1, 16-21, and 30-41 are pending.
Claims 1, 16-21, and 30-39 are rejected.
Claims 40 and 41 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
PAUL J HOLLAND whose telephone number is (571)270-3537. The examiner can normally be reached on Monday to Friday from 8AM to 5PM.
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/PAUL J HOLLAND/Primary Examiner, Art Unit 1656