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 .
DETAILED ACTION
This application is in response to the papers filed on August 24, 2026. Claims 36-66 are currently pending as per claims filed on August 24, 2026. Claims 36, 53, and 66 have been amended in Applicant’s amendment filed August 24, 2026.
Election/Restrictions
Applicant’s election without traverse of the invention of Group I, claims 36-53, drawn to an expression construct, in the reply filed on August 24, 2026 in response to the restriction requirement filed on June 23, 2026 is acknowledged.
Claims 54-66 are withdrawn from further consideration by the Examiner, pursuant to 37 CFR 1.142(b), as being drawn to non-elected inventions, there being no allowable generic or linking claim. Claims drawn to non-elected inventions will be withdrawn during prosecution. The requirement for restriction between Groups I-III is maintained for reasons of record, and hereby made FINAL. Applicant timely responded to the restriction (election) requirement in the correspondence filed on August 24, 2026.
Therefore, claims 36-53 are currently under examination to which the following grounds of rejection are applicable.
Priority
The present application is a 35 U.S.C. 371 national stage filing of the International Application No. PCT/IB2022/056458, filed July 13, 2022. Applicant’s claim for the benefit of a prior-filed parent provisional application 63/221,883 filed on July 14, 2021 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Thus, the earliest possible priority for the instant application is July 14, 2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on January 11, 2024, November 11, 2024, and May 21, 2026 were filed. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Specification
Cross-Reference to Related Applications
The disclosure filed on January 11, 2024 is objected to because the cross-reference to related applications on the first page of the specification is not provided. The cross-reference should contain the priority applications listed above in addition to the respective patent numbers. Correction is required.
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.
Claims 36, 48, and 49 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Boye at al. (US 2022/0133909 A1).
Regarding claim 36, Boye teaches AAV expression constructs that comprise heterologous nucleic acid sequences wherein the heterologous nucleic acid sequence comprises a GUCY2D sequence in which “a replacement coding sequence is administered to the subject to provide a functional protein, e.g., GUCY2D, to restore, e.g., completely or partially, photoreceptor function to a subject (e.g., a human).” (par 0082-0084). Furthermore, the nucleic acid sequence is operably linked to a CMV promoter, and the construct further comprises the expression control sequence of a polyadenylation sequence. (par 0036; 0079). In reference to instant SEQ ID NO: 9, Boye teaches SEQ ID No: 9 (encodes for GUCY2D) that is 100% identical (the full alignment is provided with the Office Action, Result # 1 duplicate result).
Regarding claims 48 and 49, Boye teaches the expression construct includes other regulatory elements including WPRE (par 0078).
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 37 and 39 are rejected under 35 U.S.C. 103 as being unpatentable over Boye at al. (US 2022/0133909 A1) as applied to claims 36, 48 and 49, further in view of Constable et al. (US 2013/0323302 A1).
The teachings of Boye are discussed supra.
Regarding claims 37 and 39, Boye teaches an expression construct comprising a CMV promoter, a nucleic acid sequence encoding retinal membrane guanylyl cyclase 1 (RetGC1), wherein the nucleic acid sequence comprises a sequence that is 100% identical to instant SEQ ID NO: 9, a polyadenylation signal, and wherein the nucleic acid sequence is operably linked to the promoter.
Boye does not teach wherein the promoter sequence comprises a sequence that is at least 90% identical to SEQ IDNO: 8.
Constable teaches recombinant virus vectors administered to the retina for treatment of ocular diseases, e.g. age-related macular degeneration (AMD), wherein the vector employs a CMV promoter that is operable linked to a transgene (par 0067-69). In reference to instant SEQ ID NO: 8, Boye teaches SEQ ID No: 21 (encodes for CMV) that is 100% identical (the full alignment is provided with the Office Action, Result # 1 duplicate result) (par 0236).
It would have been prima facie obvious for one of ordinary skill in the art at the time of the effective filing date to have modified construct taught by Boye et al. to include the CMV as taught by Constable et al. because it would have been obvious to combine prior art elements according to known methods to yield predictable results. The inclusion of the CMV promoter sequence with the expression construct would have led to predictable results with a reasonable expectation of success because both Boye et al. and Constable et al. teach vectors wherein the transgene is operably linked with a CMV promoter, and furthermore Constable et al. teaches these vectors in the context of treating ocular diseases for which the instant claims are in relation to. Altogether, it would have been obvious to have included the CMV sequence taught by Constable et al. with the expression construct taught by Boye et al.
Claims 43 and 44 are rejected under 35 U.S.C. 103 as being unpatentable over Boye at al. (US 2022/0133909 A1) as applied to claim 36, 48, and 49, further in view of Neitz et al. (US 2012/0172419 A1).
The teachings of Boye are discussed supra.
Regarding claims 43 and 44, Boye teaches an expression construct comprising a CMV promoter, a nucleic acid sequence encoding retinal membrane guanylyl cyclase 1 (RetGC1), wherein the nucleic acid sequence comprises a sequence that is 100% identical to instant SEQ ID NO: 9, a polyadenylation signal, and wherein the nucleic acid sequence is operably linked to the promoter.
Boye does not teach wherein the nucleic acid sequence encoding the RetGC1 encodes a protein comprising a sequence that is at least 90% identical to SEQ ID NO: 12.
Neitz teaches a gene delivery vector that encodes SEQ ID NO: 25, a retina specific guanylate cyclase (GUCY2D) (NP_000171.1) that is 100% identical to instant SEQ ID NO: 12, wherein the gene is operatively linked to a promoter and to be expressed in cone cells for treating cone cell disorders (the full alignment is provided with the Office Action, Result # 1 duplicate result) (par 0042-0043, 0054)
It would have been prima facie obvious for one of ordinary skill in the art at the time of the effective filing date to have modified construct taught by Boye et al. by teaching the nucleic acid sequence that encodes GUCY2D as being that of SEQ ID NO: 12 based on the protein sequence, i.e. RetGC1, being well-known in the art prior to the filing of the claimed invention, as seen by the teachings of Neitz et al. SEQ ID NO: 25. Therefore, the inclusion of such sequence that is expressed by the expression construct taught by Boye et al. would be an obvious choice as both the nucleic acid and amino acid sequences are known.
Claims 45-47 are rejected under 35 U.S.C. 103 as being unpatentable over Boye at al. (US 2022/0133909 A1) as applied to claim 36, 48, and 49, further in view of Bell et al. (US 2022/0154210 A1).
The teachings of Boye are discussed supra.
Regarding claims 45-47, Boye teaches an expression construct comprising a CMV promoter, a nucleic acid sequence encoding retinal membrane guanylyl cyclase 1 (RetGC1), wherein the nucleic acid sequence comprises a sequence that is 100% identical to instant SEQ ID NO: 9, a polyadenylation signal, and wherein the nucleic acid sequence is operably linked to the promoter.
Boye does not teach wherein the polyadenylation signal comprises a bovine growth hormone polyadenylation (BGHpolyA) signal, and more specifically wherein the polyadenylation signal comprises SEQ ID NO: 11.
Bell teaches “recombinant viral vectors and methods of using recombinant viral vectors to express proteins in the retina, e.g., retinal pigment epithelium (RPE) cells, of subjects suffering from retinal diseases and blindness, e.g., BCD... The present invention also relates to viral vectors that are capable of directing a heterologous gene to the retina, e.g., RPE cells of the retina.” (par 0006-0007). The viral vectors employed use the Bovine Growth Hormone (bGH) polyA signal sequence wherein the observed outcomes when using this sequence were increased expression of the transgene in the retina (Example 2). Bell teaches SEQ ID NO: 18, a BGH polyA signal sequence, that is 100% identical to instant SEQ ID NO: 11 (the full alignment is provided with the Office Action, Result #9) (par 0044).
It would have been prima facie obvious for one of ordinary skill in the art at the time of the invention to have modified the expression construct that comprises a polyA sequence as taught by Boye by incorporating the claimed BGH polyA because it would have been obvious to substitute one known element for another to obtain predictable results. Substituting the polyA in the composition of Boye for the claimed BGH polyA sequence as taught by Bell would have led to predictable results with a reasonable expectation of success because Bell teaches improved outcomes when using BGH as seen in increased expression when an expression construct with BGH was delivered and expressed in the retina. Furthermore, the expression construct taught by Boye comprises RetGC1 which is intended to restore photoreceptor function (par 0025), and therefore there is clear motivation to include the BGH sequence which improves outcomes of expression in the retina for effective treatment of retinal related diseases or disorders.
Claims 50-51 are rejected under 35 U.S.C. 103 as being unpatentable over Boye at al. (US 2022/0133909 A1) as applied to claim 36, 48, and 49, further in view of Miyazaki et al. (US 8,278,284 B2).
The teachings of Boye are discussed supra.
Regarding claims 50-51, Boye teaches an expression construct comprising a CMV promoter, a nucleic acid sequence encoding retinal membrane guanylyl cyclase 1 (RetGC1), wherein the nucleic acid sequence comprises a sequence that is 100% identical to instant SEQ ID NO: 9, a polyadenylation signal, and wherein the nucleic acid sequence is operably linked to the promoter. Boye further teaches the expression construct includes other regulatory elements including WPRE (par 0078).
Boye does not teach wherein the posttranscriptional regulatory element comprises SEQ ID NO: 10.
Miyazaki teaches vectors that are administered to the retina for stable expression of a therapeutic gene wherein the vector comprises the woodchuck hepatitis virus posttranscriptional regulatory element (WPRE) sequence( col 4, ln 3-7, 26-31). The outcomes of using the WPRE sequence revealed increased protein expression when compared to the control. (Example 2). Miyazaki teaches SEQ ID NO: 11, a WPRE sequence, that is 100% identical to instant SEQ ID NO: 10 (the full alignment is provided with the Office Action, Result #3) (col 12, ln 63-64).
It would have been prima facie obvious for one of ordinary skill in the art at the time of the invention to have modified the expression construct that comprises a WPRE sequence as taught by Boye by incorporating the claimed WPRE because it would have been obvious to substitute one known element for another to obtain predictable results. Substituting the WPRE in the composition of Boye for the claimed WPRE sequence as taught by Miyazaki would have led to predictable results with a reasonable expectation of success because Miyazaki teaches improved outcomes when using the sequence as seen in increased protein expression (Example 2).
Conclusion
Claims 38, 40-42, and 52-53 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. SEQ ID NOs: 1-4, 7, 13, and 14 are free of the prior art at the respective claimed sequence identities.
Claims 36-37, 39, 43-51 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL A RIGA whose telephone number is (571)270-0984. The examiner can normally be reached Monday-Friday (8AM-6PM).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria G Leavitt can be reached at (571) 272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MICHAEL ANGELO RIGA/ Examiner, Art Unit 1634
/TERESA E KNIGHT/ Primary Examiner, Art Unit 1634
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