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 .
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-11) in the reply filed on 09/12/2025 is acknowledged.
Claims 12-25 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Election was made without traverse in the reply filed on 09/25/2025. Therefore, claims
1-11 are currently under examination
Priority
Applicants’ claim for the benefit of a prior-filed application parent provisional application 62992671 filed on 03/20/ 2020 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) was filed before the mailing date of the non-final first action on the merits. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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.
Claims 1-9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bjorklund et al ( WO 2019/158619 A1).
Regarding claim 1, Bjorklund et al disclose a method for designing and manufacturing a library of modified viral vectors comprising a modified capsid protein, wherein the modified capsid is generated by inserting a polynucleotide fragment in the capsid gene. Bjorklund et al teach that the said insertion generates a viral capsid with increased tropism and/or infectivity for a given cell type. (See page 12 lines 27-35). Bjorklund et al also disclose a method for identifying an engineered capsid protein exhibiting a preferential tropism to a desired cell type. Also provided is a method of improving tropism of a viral vector or particle toward a target cell. ( See page14, lines 25-27; and page 6, lines 7-8). According to Bjorklund et al, the modified viral particles may encapsulate a transgene and a barcode polynucleotide (i.e. identifier sequence) to be delivered to a target cell, wherein the transgene and the barcode polynucleotide may be inserted in the viral genome, i.e. between the terminal repeat sequences, this reads on step (a) of instant claim. (See page 35, line 8, and page 20, lines 20-21). The method of Bjorklund also involves a step of identifying a capsid protein that exhibit a preferential tropism to a desired cell type, which is achieved by contacting a cell population with the modified viral vectors either in vivo or in vitro, this reads on step (b) of instant claim. ( See page 29 lines 27-32, and page 30, lines 1-3). Bjorklund et al also teach a step of determining the sequence of the barcode to identify the capsid protein present in each cell type, and thereby identifying the candidate polynucleotides(i.e. the polynucleotide fragment that was inserted in the capsid gene) responsible for the desired tropism and the corresponding candidate polypeptides, this reads on step (c) and (e) of instant claim. ( See page 19, lines 14-32). The method of Bjorklund also involves the step of determining the cell type of each transduced cell from (b) by monitoring marker expression and selecting the cells wherein marker expression follows a desired pattern, this reads on step (d) of instant claim.(See page 30, lines 1-11, and lines 28-31).
Regarding claim 2, Bjorklund et al also disclose a method for identifying a capsid protein that exhibits a preferential tropism to a desired cell type. The method involves using a barcode polynucleotide (i.e. sequence identifier) whose sequence of which is not naturally present in the host cell, and then operably linking the barcode polynucleotide to the polynucleotide fragment to be inserted into the capsid gene. As such, identification of the barcode polynucleotide (i.e. by RNA sequencing) would allow for the identification of the inserted polynucleotides fragment or the corresponding polypeptide fragment that is responsible for the desired tropism. (See claim 4, page 19, lines 13-25, and page 30, lines 9 -15).
Regarding claim 3, Bjorklund et al also disclose a method of determining the cell type using the method of transcriptional profiling. For example, Bjorklund et al state that the method also involves the step of “ identifying the candidate polynucleotides in the target cells having an expression profile of the marker corresponding to the desired property. (See page 6, line 32-35, and page 7 , line 1-2).
Regarding claim 4, Bjorklund et al disclose that the viral vector contain a transgene encoding a detectable marker (e.g. reporter). ( See page 2 ,lines 28-29).
Regarding claim 5, Bjorklund et al also disclose utilizing a transgene encoding for a reporter protein to identify cells transduced with an r AAV. The identification method of Bjorklund, for example, involves contacting a cell population with viral vectors comprising of a modified viral capsid encapsulating a transgene encoding for a reporter, and then a method of monitoring the reporter expression and selecting the cells wherein marker expression follows a desired pattern. ( See page 3, lines 5-12).
Regarding claim 6, Bjorklund et state that “ The cells to be targeted for transgene delivery are preferably cells in which expression of the transgene is desired. The target cells may for example be neurons”. (See page 35 lines 12-13).
Regarding claim 7, Bjorklund et al also disclose generating a viral particle comprising modified viral capsid ( termed as AAV-MNM001-024) which display an improved tropism to primary glial cells, including astrocytes and microglia. (See page 54, lines 21-25).
Regarding claim 8, Bjorklund et al further disclose that the engineered capsid protein is generated by inserting a polynucleotide fragment within the capsid gene so that it can be transcribed and translated into a polypeptide fragment displayed on the capsid. ( See page 15 lines 25-36, and page 16 lines 1-3).
Regarding claim 9, Bjorklund et al state that the “ The insertion site may be
at the N-terminus of VP2. It may also be at the vertices of the assembled capsid, e.g. centered around amino acid residue 587 of the Cap gene of AAV2 or around amino acid residue 588 of the AAV9 cap gene.”
Claim Rejections - 35 USC § 103
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-11 are rejected under 35 U.S.C. 103 as being unpatentable over Bjorklund et al ( WO 2019/158619 A1), in view of Boye et al (US 2016/0369299 A1).
The teachings of Bjorklund et al are set forth above. Bjorklund et al anticipates claims 1-9.
Regarding claim 10-11, following the discussion above. Bjorklund teach a method of engineering a modified capsid protein displaying a preferential tropism to a desired cell type. However, Bjorklund et al do not teach generating a modified capsid protein comprising of an AAV2 capsid protein containing the Y444F, Y500F, Y730F, T491V, R585S, R588T, R487G amino acid substitutions or a combination thereof.
Boye et al teach an a rAAV viral vector comprising an engineered capsid protein, wherein the engineered capsid protein is an AAV2 capsid protein containing the amino acid substitutions of Y444F, Y500F ,T491V, R585S, R588T, R487G, and Y730F. According to Boye et al, a rAAV vector harboring the engineered capsid protein with such amino acid substitutions has an enhanced ability to selectively and exclusively target photoreceptors or retinal pigmented epithelial cells (RPE). (See paragraphs [0009],[0014], and [0018-0019]. Therefore, claims 10-11 would have been obvious to one of ordinary skill in the art, as there was some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. Because Bjorklund et al teach a method for engineering a modified capsid protein with a preferential tropism to a desired cell type using the method a peptide insertion. Boye et al teach an engineered AAV2 capsid protein with enhanced tropism to photoreceptors and RPE cells. Thus, it would have been obvious to one with ordinary skill in the art at the time the invention was filed to modify the teachings of Bjorklund and Boye et al and engineer an AAV2 capsid comprising the amino acid substitutions of Boye et al. There would be a reasonable expectation of success in doing so will generate a rAAV viral vector for targeting photoreceptor and RPE cells.
Conclusion
No claim is allowed.
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/FATIMAH KHALAF MATALKAH/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638