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 .
Disposition of Claims
Claims 1-2, 6, 8-12, 17-18, 20, 23-24, 26, 28-29, 40, 49, 52, and 54 are pending.
Examiner’s Note
All paragraph numbers (¶) throughout this office action, unless otherwise noted, are from the US PGPub of this application US 2023/0265455 A1, Published 24 August 2023. Applicant’s amended Specification as presented on 24 January 2023 is acknowledged and entered.
Applicant is encouraged to utilize the new web-based Automated Interview Request (AIR) tool for submitting interview requests; more information can be found at https://www.uspto.gov/patent/laws-and-regulations/interview-practice.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
The information disclosure statement (IDS) submitted on 19 July 2023 has been considered, as a whole, by the examiner. Any individual references with strikethroughs, however, have not been considered.
Specification; Sequence Disclosure Requirements
This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 through 1.825 for the reason(s) set forth below or on the attached Notice To Comply With Requirements For Patent Applications Containing Nucleotide Sequence And/Or Amino Acid Sequence Disclosures.
The specification is objected to because Paragraph 0134 of the PGPub of the instant application comprises two sequences which are identical in length at 4549 bp and which are both identified as corresponding to SEQ ID NO: 33. They have different names, however. The first is labelled as pTR-X002-3p. The second is labelled as pTR-X002-3pSR. It is unclear if one name is simply a typographical error. If not, it is unclear why the same sequence would have two different names and why the two sequences would be listed separately if they are in fact one and the same.
Applicants must comply with sequence rules in order to be considered a complete response to this Office Action.
Specification
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections
Claims 10 and 17 are objected to because of the following informalities: In Claim 10, it is suggested that it say “The AAV vector of claim 9” instead of “The rAAV vector of claim 9”.
In Claim 17, the “%” in “80%” was accidentally deleted in the most recent claim set.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b); Second Paragraph
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.
Claim 9 is 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.
Claim 9 recites the limitation "The rAAV vector" in Line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 9 is dependent on Claim 1, but Claim 1 does not introduce the limitation of an rAAV vector. Claim 1 recites an AAV vector. As such, it is unclear which rAAV Claim 9 is referring to. This lack of clarity renders the claim indefinite. It is suggested that the claim be amended by replacing “rAAV vector” with “AAV vector”, but Applicant is free to amend the claim as they deem necessary.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claim 9 is rejected on the grounds of being indefinite.
Claims 40 and 49 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 40 and 49, they both recite the limitation of “an AAV44.9(E531D) capsid”. It is unclear if the recited element within parentheses is a required element of the claim. It is suggested that the Applicant amend the claim to either remove the parentheses or amend the claims to recite the items within the parentheses as additional dependent claims which further limit the independent, parent claim. Alternatively, the claims can be amended to recite “an AAV44.9 capsid comprising an E531D mutation”, but Applicant is free to amend the claims as they deem necessary.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claim 40 and 49 are rejected on the grounds of being indefinite.
Claims 52 and 54 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 Claims 52 and 54, they are both dependent upon Claim 48, which was cancelled in the most recent claim set. As such, it is unclear which claim they are referring to and this lack of clarity renders the claims indefinite. It is suggested that the claims be amended to be dependent on Claim 49, but Applicant is free to amend the claims as they deem necessary.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claim 52 and 54 are rejected on the grounds of being indefinite.
Claim Interpretation
In light of the issues raised above, the claims are being interpreted as reading upon the following:
Claim 1 is drawn to an adeno-associated virus (AAV) vector comprising a polynucleotide that comprises (i) a heterologous nucleic acid encoding a retinoschisin protein, (ii) an intron, splice donor region, splice acceptor region, or any combination thereof and (iii) a nucleic acid stuffer sequence positioned 3' of the heterologous nucleic acid, wherein the nucleic acid stuffer sequence has a length of about 100 to about 3000 nucleotides.
Claim 17 is drawn to a recombinant AAV (rAAV) vector comprising a polynucleotide that comprises a heterologous nucleic acid comprising a sequence having at least 80% identity to the nucleotide sequence of SEQ ID NO: 8, wherein the heterologous nucleic acid is operably linked to one or more regulatory elements that direct expression of the heterologous nucleic acid in a photoreceptor cell or retinal pigment epithelium cell.
Claim 49 is drawn to a method for treating or ameliorating X-linked retinoschisis (XLRS) in a mammal, the method comprising subretinally administering to one or both eyes of the mammal an rAAV particle comprising a polynucleotide that comprises a heterologous nucleic acid encoding a retinoschisin protein and an AAV44.9 capsid comprising an E531D mutation in an amount sufficient to treat or ameliorate the one or more symptoms of the retinoschisis in the mammal.
Further limitations on the AAV vector according to Claim 1 are:
2. The AAV vector of claim 1, comprising the intron, wherein the intron comprises a splice donor region and/or a splice acceptor region.
6. The AAV vector of any one of claim 1, comprising a post- transcription regulatory element.
8. The AAV vector of claim 6, wherein the post-transcription regulatory element comprises a woodchuck hepatitis virus post-transcription regulatory element (WPRE).
9. The AAV vector of claim 1, further comprising a polyadenylation signal.
10. The AAV vector of 9, wherein the nucleic acid stuffer sequence is positioned 3' of the polyadenylation signal.
11. The AAV vector of 1, wherein the retinoschisin protein is a human retinoschisin protein.
12. The AAV vector of 1, wherein the heterologous nucleic acid does not comprise the 5' untranslated region of human retinoschisin, the 3' untranslated region of human retinoschisin, or both the 5' untranslated region of human retinoschisin and the 3' untranslated region of human retinoschisin.
Further limitations on the rAAV vector according to Claim 17 are:
18. The rAAV vector of claim 17, wherein the polynucleotide comprises a post-transcription regulatory element.
20. The rAAV vector of claim 18, wherein the post-transcription regulatory element is positioned 3' of the heterologous nucleic acid.
23. The rAAV vector of claim 17, wherein the heterologous nucleic acid comprises the sequence set forth as SEQ ID NO: 9.
24. The rAAV vector of claim 17, wherein the polynucleotide comprises the sequence of SEQ ID NO: 10.
26. The rAAV vector of claim 17, wherein the polynucleotide comprises a promoter that is capable of expressing the nucleic acid sequence in one or more photoreceptors or retinal pigment epithelial cells of a mammalian eye.
28. The rAAV vector of claim 26, wherein the promoter is a human rhodopsin kinase (hGRK1) promoter.
29. The rAAV vector of claim 17, wherein the vector is self-complementary.
40. A recombinant adeno-associated viral (rAAV) particle comprising an AAV44.9 capsid comprising an E531D mutation and the rAAV vector claim 17.
Further limitations on the method according to Claim 49 are:
52. The method of claim 49, wherein the step of administering a) preserves one or more photoreceptor cells, b) restores laminar retinal structure, c) restores one or more rod- and/or cone-mediated functions, d) restores completely or partially visual behavior in one or both eyes, or e) any combination thereof.
54. The method of claim 49, wherein the step of administering comprises subretinal administration to a fovea of one or both eyes of the mammal.
Claim Rejections - 35 USC § 112(a); 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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 17-18, 20, 23-24, 26, 28-29, and 40 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The instant application attempts to tie function to sequence identity in the context of a recombinant AAV (rAAV) vector comprising a polynucleotide that comprises a heterologous nucleic acid comprising a sequence having at least 80% identity to the nucleotide sequence of SEQ ID NO: 8, wherein the heterologous nucleic acid is operably linked to one or more regulatory elements that direct expression of the heterologous nucleic acid in a photoreceptor cell or retinal pigment epithelium cell. While a percent identity threshold is provided in the claims and Paragraph 0065 states that “the heterologous nucleic acid differs by 5, 10, 15, 20, 25, or more than 25 nucleotides from the nucleotide sequence of SEQ ID NO: 8”, the instant specification fails to identify which region or regions are able to tolerate such changes. Paragraphs 0073-0074 state that the polynucleotides disclosed may comprise 1-18 nucleotides that differ relative to SEQ ID NO: 8 or may comprise 1-12, or more, silent mutations. Paragraph 0074 also states that the heterologous nucleic acid may vary in identity of up to 30% relative to SEQ ID NO: 8. Despite this additional language, Applicant still fails to identify the critical or essential nucleotides which cannot tolerate such variation. The specification also does not mention conservative substitutions in the context of SEQ ID NO: 8, or at all for that matter. Additionally, Claim 17, as currently written, does not specify that it is reading on only silent mutations. As such, the claimed variants encompassed by the claim language include variants with non-conservative substitutions. Thus, it would be unclear to a person having ordinary skill in the art to know what to change and what not to change.
Furthermore, while it is not explicitly states, it is assumed that the sequence corresponding to SEQ ID NO: 8 shown in the data provided has a sequence that is 100% identical to the claimed sequence. Even if that is not the case, the data shown do not explicitly include any claimed variants having as little as 80% sequence identity, or even 81-99% sequence identity, raising questions about how effective these claimed variants would be in the experiments performed. Thus, it is not clear what was tested, it does not appear that any claimed variants were tested, and the essential characteristics of the genus Applicant is claiming have not been identified or disclosed.
As such, it does not appear Applicant was in possession of the full scope of the claimed invention at the time of filing and thus Claims 17-18, 20, 23-24, 26, 28-29, and 40 do not meet the written description requirement.
Claim Rejections - 35 USC § 102
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 17-18, 20, 26, and 28-29 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Sieving et al. (US 2016/0002666 A1) (cited on IDS by Applicant as U.S. Patent No. 9,873,893 B2)
Sieving et al. teach a self-complementary AAV (scAAV) expressing a heterologous nucleic acid encoding human retinoschisin under the control of an eye-specific promoter, such as a rhodopsin kinase promoter, which allows for expression of the therapeutic protein in cells such as photoreceptor cells (see Paragraphs 0012-0013, 0046, 0078, 0102-0103, 0105, 0107), which reads on instant Claims 17, 26, and 28-29. Sieving et al. also teach wherein said scAAV expressing said heterologous nucleic acid also comprises a post-transcription regulatory element and wherein said element is located 3’ of the heterologous nucleic acid (see Paragraphs 0015, 0102, 0104), which reads on instant Claims 18 and 20. Additionally, Sieving et al. teach SEQ ID NO: 1, which is 100% identical to instant SEQ ID NO: 8 (see Sequence Listing), which reads on instant Claim 17.
For at least these reasons, Sieving et al. teach the limitations of instant Claims 17-18, 20, 26, and 28-29 and anticipate the invention encompassed by said claims.
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.
Claims 1-2, 6, and 8-12 are rejected under 35 U.S.C. 103 as being unpatentable over LaCroix-Desmazes et al. (US 2021/0228738 A1) and O’Riordan and Adamowicz (US 2017/0173183 A1).
LaCroix-Desmazes et al. teach a viral vector, such as AAV, comprising a heterologous polynucleotide encoding a therapeutic molecule, including human retinoschisin (see Paragraphs 0012, 0017, 0049), which reads on instant Claims 1 and 11. LaCroix-Desmazes also teach wherein said viral vector comprises an expression cassette comprising elements such an intron, a polyadenylation signal, and a WPRE post-transcription regulatory element (see Paragraphs 0096, 0114, 0128, 0212), which reads on instant Claims 1-2, 6, and 8-9.
O’Riordan and Adamowicz teach AAV comprising an intron and a polyadenylation signal, wherein said intron comprises a splice donor region and a splice acceptor region (see Paragraphs 0119, 0122, 0138), which reads on instant Claims 1-2 and 9. O’Riordan and Adamowicz also teach AAV comprising stuffer sequences which are on the 3’ side of a heterologous nucleic acid and on the 3’ side of the polyadenylation signal, wherein said stuffer sequence corresponds to reference SEQ ID NO: 11 and is 2239 nucleotides long (see Paragraph 0119, 0121; Sequence Listing), which reads on instant Claims 1, 10. Additionally, O’Riordan and Adamowicz teach AAV expressing human rhodopsin cDNA which does not contain the one or both the 5’ and 3’ untranslated regions (UTRs) (see Paragraphs 0051, 0138; Figure 17), which reads on instant Claim 12. While O’Riordan and Adamowicz focus on rhodopsin, this approach could potentially be used for any therapeutic protein introduced via AAV.
A person having ordinary skill in the art would have been motivated to combine the teachings of LaCroix-Desmazes et al. and O’Riordan and Adamowicz in order to develop an AAV vector expressing a heterologous nucleic acid. The regulatory elements disclosed by both LaCroix-Desmazes and O’Riordan and Adamowicz would allow for proper expression of the human retinoschisin protein disclosed by LaCroix-Desmazes et al. The use of stuffer sequences and/or cDNA encoding a therapeutic protein, such as retinoschisin, lacking the untranslated regions, as disclosed by O’Riordan and Adamowicz would allow for the expression cassette of LaCroix-Desmazes to be the proper size for packaging in the disclosed AAV vector, which would increase packaging efficiency and increase the number of AAV vectors produced containing the therapeutic protein.
Such modifications, combining prior art elements according to known methods to yield predictable results, would have had a reasonable expectation of success and arrived at the claimed invention prior to the effective filing date of the instant application. For at least these reasons, instant Claims 1-2, 6, and 8-12 are rejected under 35 U.S.C. 103 as being unpatentable over the prior art.
Claims 23-24 and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Sieving et al. (US 2016/0002666 A1) (cited on IDS by Applicant as U.S. Patent No. 9,873,893 B2) as applied to claims 17-18, 20, 26, and 28-29 above, and further in view of Gray (US 2018/0305715 A1), Xie and Guo (US 2022/0403417 A1), LaCroix-Desmazes et al. (US 2021/0228738 A1), and Dyka and Hauswirth (US 2022/0175969 A1)
The applied secondary reference, Dyka and Hauswirth (US 2022/0175969 A1), has a common Assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
The previous teachings of Sieving et al. have been summarized above.
Sieving et al. teach SEQ ID NO: 1, as noted above, which is also 90.8% identical to instant SEQ ID NO: 9 and 89.2% identical to instant SEQ ID NO: 10 (see Sequence Listing), which reads on instant Claims 23-24.
Gray teaches AAV particles comprising a heterologous polynucleotide, wherein said heterologous polynucleotide encodes a polypeptide, such as retinoschisin (see Paragraphs 0105, 0109), which reads on instant Claims 17 and 23-24.
Xie and Guo teach codon optimization of a gene of interest being delivered by an rAAV vector in which the codon optimization reduces the number of CpG dinucleotide islands (see Paragraphs 0025, 0028-0029), which reads on instant Claim 23.
The previous teachings of LaCroix-Desmazes have been summarized above. They also teach an AAV vector comprising a heterologous polynucleotide encoding polypeptides, wherein said polypeptides can comprise a tag, such as a myc tag (see Paragraphs 0049, 0194), which reads on instant Claim 24.
Dyka and Hauswirth teach vector constructs comprising transgenes, wherein said vector construct is a viral vector, such as rAAV (see Abstract; Paragraph 0007). Dyka and Hauswirth also teach that these vector constructs are polynucleotides which are encapsidated by viral capsids, that these viral capsids form rAAV particles, and that these rAAV particles can be of any serotype, including variants, derivatives, and pseudotypes such as AAV44.9 and AAV44.9(E531D) (see Paragraphs 0080-0083), which reads on instant Claim 40.
A person having ordinary skill in the art would have been motivated to modify the teachings of Sieving et al. with those of Gray, Xie and Guo, LaCroix-Desmazes et al., and Dyka and Hauswirth in order to generate an rAAV expressing retinoschisin. The capsid variants disclosed by Dyka and Hauswirth would enable better expression in the eye for retinoschisin, as disclosed by Sieving et al. and Gray, in the rAAV disclosed by Sieving et al. using an eye-specific promoter, as also disclosed by Sieving et al. The codon optimization technique disclosed by Xie and Guo reduces the number of structural elements, such as CpG islands, which may be immunogenic in a mammalian host. This would make the polynucleotide encoding the therapeutic protein less immunogenic and thus safer for administration to subjects. The inclusion of a myc tag, as disclosed by LaCroix-Desmazes et al., would be useful in the potential purification and/or detection of the polypeptide. The combination of these references would lead a person having ordinary skill to the instant SEQ ID NOs: 9 and 10 and as such they would be rendered obvious over these prior art references as the modifications to SEQ ID NO: 1 of Sieving et al., which is 100% identical to instant SEQ ID NO: 8 and instant SEQ ID NOs: 9 and 10 are simply variants of instant SEQ ID NO: 8 (instant Claims 23-24).
Such modifications, combining prior art elements according to known methods to yield predictable results, would have had a reasonable expectation of success and arrived at the claimed invention prior to the effective filing date of the instant application. For at least these reasons, instant Claims 23-24 and 40 are rejected under 35 U.S.C. 103 as being unpatentable over the prior art.
Claims 49, 52, and 54 are rejected under 35 U.S.C. 103 as being unpatentable over Sieving et al. (US 2016/0002666 A1) (cited on IDS by Applicant as U.S. Patent No. 9,873,893 B2), Boye et al. (2020) (cited on IDS by Applicant), Dyka and Hauswirth (US 2022/0175969 A1).
The applied secondary reference, Dyka and Hauswirth (US 2022/0175969 A1), has a common Assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
The previous teachings of Sieving et al. have been summarized above. Sieving et al. also teach a method of treating X-linked retinoschisis (XLRS) in a human comprising administering to said human a therapeutically effective amount of an expression vector comprising: a capsid protein from AAV and an expression cassette encoding retinoschisin protein, wherein the vector is administered subretinally (see Abstract; Paragraphs 0014, 0017, 0020), which reads on instant Claims 49, 52, and 54. Additionally, Sieving et al. teach a method wherein the rAAV vector is administered to one or both eyes and wherein administering results in preserved retinal function and structure (see Paragraphs 0042, 0084, 0098-0101), which reads on instant Claims 49 and 52.
The previous teachings of Dyka and Hauswirth have been summarized above, including the use of AAV serotypes, including variants, derivatives, and pseudotypes such as AAV44.9 and AAV44.9(E531D) (see Paragraphs 0080-0083), which reads on instant Claim 49.
Boye et al. teach a method for treating inherited retinal diseases (IRDs) in a subject using gene therapy, including rAAV vectors (see Page 1464, Left Column, Last Paragraph), which reads on instant Claim 49. Boye et al. also teach a method wherein administering a vector, specifically AAV44.9(E531D), subretinally to a fovea of one or both eyes of a mammal resulted in restoration of both cone and rod function (see Abstract; Page 1465, Left Column, Paragraph 2), which reads on instant Claims 49, 52, and 54.
A person having ordinary skill in the art would have been motivated to combine the teachings of Sieving et al., Dyka and Hauswirth, and Boye et al. in order to develop a method for treating XLRS. The capsid variants disclosed by Dyka and Hauswirth and Boye et al. would enable better expression in the eye for retinoschisin, as disclosed by Sieving et al. using an eye-specific promoter, as also disclosed by Sieving et al. These capsid variants would also allow for better transduction of the eyes, which would make the greatly enhance the therapeutic effect of the rAAV expressing retinoschisin of Sieving et al. and make it more cost effective to use in gene therapy.
Such modifications, combining prior art elements according to known methods to yield predictable results, would have had a reasonable expectation of success and arrived at the claimed invention prior to the effective filing date of the claimed invention. For at least these reasons, instant Claims 49, 52, and 54 are rejected under 35 U.S.C. 103 as being unpatentable over the prior art.
Conclusion
No claims are allowed.
The prior art made of record, but not relied upon, and considered pertinent to applicant's disclosure is listed below:
Cronin et al. (U.S. Patent No. 9,567,376 B2)
Cronin et al. disclose capsid proteins and AAV capable of targeting various types of ocular cells and methods of treating various ocular disorders by administering compositions comprising said AAV. This reference has not been utilized, as rejection would have been redundant to those set forth above.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAREY A STUART whose telephone number is (703)756-4668. The examiner can normally be reached Monday - Friday, 7:30 AM - 4:30 PM EST.
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/CAREY ALEXANDER STUART/Examiner, Art Unit 1671
/JANET L ANDRES/Supervisory Patent Examiner, Art Unit 1671