DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This office action is in response to an amendment filed 4/8/2026.
Claims 1, 22, 27, 29, 30, 32, 34, 36 and 38-40 are pending. Claims 29, 30, 32, 34, 36 and 38-40 are withdrawn from examination as directed to non-elected subject matter.
This application is a 371 filing of PCT/US2020/056156 filed 10/16/2020 which claims the benefit of priority of U.S. Provisional Application No. 62/916,396, filed October 17, 2019.
Response to Amendment
Applicants have not completely corrected the browser executable codes as depicted below.
The amendments are sufficient to overcome the objections to and the rejections under 35 USFC 112, second to the claims. The previous rejections under 35 USC 112, first and prior art have been overcome. However, the amendments have led to new rejections under both statutes based upon the amendment.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code in ¶ 0137 and 0196 of the provided for disclosure. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code. See MPEP § 608.01. This objection is maintained as the following two passages have not been corrected.
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Claim Rejections - 35 USC § 112, first paragraph
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 1, 22 and 27 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This amendment is restated based upon applicant’s’ amendment.
Applicants have corrected all of the issues with the claims as regard description except the following. The claims are drawn to an intron cassette that requires “a neuron specific exon sequence”. The claims omit an actual full exon by reciting “a neuron specific sequence” which entails simply a set of nucleotides. However, the sequence must exhibit a neuron specific PSI of above 30 percent and near 0 in one or more non-target cell types. This therefore means the structure must have a function. But claiming the sequence as “a sequence” does not provide any more than a dinucleotide that is required. To the contrary, the disclosure teaches that the construct comprises the exon is . Figure 1 suggests that such exons are limited in cell type to neuronal based on criteria below.
(¶0142) For the first criterion, a splicing event must be above 30 percent spliced in (PSI) in the cell type of interest and near 0 PSI in other non-target cell types that may express a SLED construct.
And those selected were shown in Table 2 wherein only cells associated with neuronal cells are provided. Hence, applicants disclosure only supports neuronal specific exons.
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Secondly, the construct is limited as comprising the exon flanked by the splice acceptor and donor. This arrangement is also critical.
The disclosure teaches a construct designed to restrict expression to particular tissues. This is accomplished by use of alternative splicing of the DNA. The intron cassette comprises a constitutive splice donor, the neuron specific exon sequence that has a frameshift mutation making it out of frame with the start codon and a constitutive splice acceptor site. In a specific mammalian cell type, the splicing will remove the exon linking the start to the gene and expression can ensue in the proper vector with a promoter that is either also cell specific or is constitutive. This arrangement is below. It is called SLED (splicing linked expression design).
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Absent this arrangement, the structures as recited will not provide the adequate function as required in the disclosure. Applicants provide “[0173] Two proof-of-concept plasmids were generated. First, a plasmid that selectively expresses GFP in neurons and a second plasmid that selectively expresses GFP in photoreceptors”. These sequences are provided on page 56. Besides this, there is only guidance on how to identify others.
So, the instant claims lack description for the following reason, the claims refer to “a neuron specific exon sequence” which is simply any sequence. Secondly, the linkage between the splice sites and the exon is critical to the function of the vector. The claims lack adequate description to link structure to the required functions. The Court indicated that while applicants are not required to disclose every species encompassed by a genus, the description of a genus is achieved by the recitation of a precise definition of a representative number of members of the genus, such as by reciting the structure. Structural features that could distinguish the compounds of the claimed genus from others not encompassed by the genus are missing from the disclosure. In this case, there are specific elements referenced but the claims reference these structures with broad generic functional terms that represent a large and diverse genus of elements. The general knowledge and level of skill in the art do not supplement the omitted description because specific, not general, guidance is needed. Since the disclosure fails to describe common attributes or characteristics that identify members of the genera, and because the process demonstrates that the genera does not exist, the claims lack adequate Written Description.
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 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.
Claims 1, 7, 12, 19, 20, 22, 27, 41, 43, 45, 50 and 57 are rejected under 35 U.S.C. 102(a)(1) unpatentable over Hagiwara and Takeuchi (US 20130137099) in view of Blencowe et al (US 20170360873). This is a new rejection necessitated by applicants’ amendment.
Hagiwara and Takeuchi teach as construct an alternative splicing reporter system that comprises a start codon (see dot in figure 6 constructs) that also comprise in order, constitutive splice sites flanking the intron cassette, a cell specific exon, wherein the start codon and the cell specific exon are out of frame. Figure 6b demonstrates the cell specificity. The construct comprises a gene of interest downstream of the intron cassette. The gene encodes a detectable moiety and is part of a vector (see below).
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Systems based on splicing dependent transcriptional gene silencing or activation are taught based in neuronal expression (see Blencowe et al ¶0217). Blencowe et al specifically teach neuronal exons with a PSI ratio above 30% in neurons (see Figure 3A, 4 and ¶0245).
Based on such teachings, it would have prima facie been obvious to one of ordinary skill in the art at the time the invention was made to use the neuronal specific exon of Blencowe in the system of Hagiwara and Takeuchi. Such a modification would have resulted in a construct encompassed by claim 1. As noted above: 1) Hagiwara and Takeuchi teach a construct for cell specific splicing wherein the vectors comprise a cell specific exon; 2) Blencowe teaches neuron specific exons with PSI of greater than 30 fold higher in neurons. Missing from Blencowe is the specifics of the construct that are claimed. Thus, a person of ordinary skill in the art, absent evidence to the contrary, would have reasonably expected that the neuronal specific exon could be used for specific expression in neurons and allow improved treatment.
Conclusion
No claims allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARIA MARVICH whose telephone number is (571)272-0774. The examiner can normally be reached 8 am - 5 pm.
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/MARIA MARVICH/ Primary Examiner, Art Unit 1634
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