Notice of Pre-AIA or AIA Status
The examiner prosecuting the application has changed.
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
Applicants’ response and claim amendments filed on 08/08/20256 are received and entered.
Claims 29-30 were cancelled on 8/2/2025. Claims 22, 27, 33-35, and 41 have been amended.
Claims 22-28 and 31-41 are pending and under consideration.
The current Application is designated as a Divisional of parent application 16314179 (now US Patent 11197936) in which claims to compositions were elected and claims to methods of treatment were initially withdrawn. However, the restriction requirement was withdrawn in the action of 4/20/2021 and the method claims were rejoined. Accordingly, the instant claims are not entitled to protection under 35 USC 120 from application of the claims of the parent patent in an obviousness type double patenting rejection.
Any rejections/objections not repeated/presented here are withdrawn.
New Rejections
Claim Rejections - 35 USC § 112
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 22-28, and 31-41 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.
Claims 22-28, and 31-41, as amended, recite a method of expressing retinol dehydrogenase 12 (RDH12) protein in the retinal photoreceptor cells of a subject, wherein the method comprises administering to the subject a recombinant adeno-associated virus (rAAV) comprising an AAV capsid protein and a nucleic acid comprising a codon optimized nucleotide sequence that has at least 90% sequence identity over the full length of SEQ ID NO: 5, wherein the nucleotide sequence encodes a functional RDH12 protein comprising the amino acid sequence set forth in SEQ ID NO: 2.
It is noted in the instant specification that SEQ ID NO: 5 comprises of 949 nucleotides. For the applicant to claim a codon optimized nucleic acid sequence of at least 90% identity over the full length of SEQ ID NO: 5, applicant would need to show possession of a sufficient number of sequence variants that have up to 94 different nucleotides, accounting for up to a 10% change of SEQ ID NO: 5 nucleotide sequences by adding, deleting, or substituting, wherein the resultant variants possess the activity of the RDH12 protein. The specification only discloses two codon optimized nucleic acid sequences (SEQ ID NO: 3 and 5). These two sequences are not sufficient to show possession of the entire genus of sequences encompassed by the claim.
While the specification discloses an example of expressing RDH12 in human COS-7 cells from a plasmid comprising a native cDNA sequence encoding RDH12, and an example of expressing RDH12 in a human induced pluripotent stem cells isolated from “a human RDH12 patient” using recombinant AAV2 carrying a native RDH12 coding sequence, the specification does not disclose an example of expressing any codon optimized RDH12 sequence, including SEQ ID NO: 5. Therefore, applicant does not show possession of a codon optimized nucleotide sequence that encodes a functional RDH12 protein comprising the amino acid sequence set forth in SEQ ID NO: 2.
The specification does not provide any identifying characteristics for the claimed genus of sequences encompassed by the claim other than the recited function of the protein. Since all the members of the claimed genus of nucleic acids will have the recited function, the recited function cannot be used as a distinguishing characteristic of the members.
In view of the foregoing, it is clear that the instant specification fails to adequately described the claimed subject matter with limitations addressed above thus the specification fails to convey that the instant co-inventors completed and had possession of the claims as now written as of the filing date sought or granted in the instant application.
Maintained Rejections
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 22-24, 26-28, 30-40 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent No. 10392622 (of record) in view of Chalberg et al., (US 20150259395).
The applied reference has a common inventor 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).
The ‘622 patent claimed expression constructs encoding RDH12 where the expression construct may be an rAAV comprising a capsid protein such as from serotype AAV1-AAV10(see claims 1-3 and 12). The rAAV comprised a 5′ AAV ITR and a 3′ AAV ITR (claim 1). The supporting specification taught “a method of treating an ocular condition in a mammalian, preferably human, subject comprises administering by intravitreal or subretinal injection to a mammalian subject in need thereof a recombinant virus as described herein” (column 26, lines 47-50) where the virus may comprise a codon-optimized transgene encoding RDH12 (column 26, line 65 to column 27, line 3). Ocular diseases include Leber’s congenital amaurosis (column 27, lines 28-36). Dosages for eye are in the range of 5e9 to 5e12 in a volume up to 1 ml (column 23, lines 36-38). The promoter may be a GRK1 promoter (column 11, lines 9-12).
The ‘622 patent did not disclose any specific nucleic acid sequence encoding RDH12.
Chalberg taught polynucleotide cassettes, expression vectors, pharmaceutically acceptable carriers comprising the vectors, and methods for the expression of a gene in cone cells by contacting cone cells in vivo with the vector (see abstract and e.g. [0175]). In one embodiment, the polynucleotide cassette comprises a sequence encoding RDH 12 (Chalberg SEQ ID NO: 47). See [0016]. The amino acid sequence of Chalberg SEQ ID NO: 47 is encoded by Chalberg SEQ ID NO: 46. This sequence has numerous regions of at least 90% identity with instant SEQ ID NO: 5, see e.g. nucleotides 1-10 which are 90% identical to SEQ ID NO: 5 nucleotides 1-10.
It would have been obvious to one of ordinary skill in the art to have used the RDH12 nucleotide sequence of Chalberg as the RDH12 coding sequence in the ‘622 patent claims. Doing so would have been no more than combining prior art elements according to known methods to yield a predictable result.
Thus the invention as a whole was prima facie obvious.
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.
Claim 41 is rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent No. 10392622 and Chalberg et al., (US 20150259395) as applied to claims 22-24, 26-28, 30-40 above, and further in view of Fotin-Mleczek et al., (US 20190241633).
The ‘622 patent and Chalberg can be combined to render obvious a method of treating an eye disease or disorder (i.e. performing a treatment on a subject with an eye disease or disorder) by administering a concentration of a recombinant AAV vector effective to result in expression of RDH12 in cone cells in a retina.
These references did not teach a nucleic acid sequence that is 90% identical to the full length of SEQ ID NO: 5.
However, Chalberg taught that different cell types and different animal species utilize tRNAs (each bearing an anticodon) coding for the same amino acids at different frequencies, therefore the coding region of the polynucleotide sequences of the invention (such as Chalberg SEQ ID NO: 46) could be codon optimized to enhance expression by replacing codons that are infrequently represented by the corresponding tRNA with more frequently represented codons. See [0160]. Accordingly, it was obvious to use codon-optimized RDH12 coding sequences in the invention of Chalberg.
Instant SEQ ID NO: 5 is about 78% identical to the wild type cDNA (instant SEQ ID NO: 1 or SEQ ID NO: 46 of Chalberg). Fotin-Mleczek taught codon optimized versions of human RDH12 (SEQ ID NOS: 35585, 48642, 61699, 22528, and 74756) that shared from 75 to 81 % identity with instant SEQ ID NO: 1 (and Chalberg SEQ ID NO: 46). Thus it was routine in the art to arrive at codon optimized versions of RDH12that were of a similar level of identity to instant SEQ ID NO: 1 as is instant SEQ ID NO:
5. While there is a very large number of sequences that can encode the amino acid sequence of instant SEQ ID NO: 2, all of these sequences could have been determined by one of ordinary skill prior to the invention since all codons were known. Moreover, not all of these sequences are adapted for expression in human cone cells, and one of ordinary skill in the art prior to the effective filing date of the claims would have been motivated by the teachings of Chalberg to optimize a native RDH12 cDNA for
expression in cone cells. To the extent that the various possible codon optimized versions of such a cDNA all encode the same polypeptide, they are considered to be obvious equivalents or alternatives of each other absent evidence of secondary considerations, such as evidence that one sequence provides superior expression to another. That is, absent evidence of secondary considerations, sequences that are 90 or 95% identical to nucleotides 1-948 of instant SEQ ID NO: 5 are considered to be obvious equivalents or alternatives of Chalberg SEQ ID NO: 46, and of Fotin-Mleczek SEQ ID NOS: 35585, 48642, 61699, 22528, and 74756. Similarly, a recombinant AAV8 comprising an expression cassette comprising those sequences under the control of a promoter active in a human photoreceptor cell, and its use in a host cell, were obvious in view of the ‘622 claims and the disclosures of Chalberg and Fotin-Mleczek.
Thus the invention as a whole was prima facie obvious.
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.
Response to Applicant’s Arguments
Applicant’s arguments filed on 8/8/2025 have been fully considered but they are not persuasive. Applicant argues that claims as currently amended recite a method of administering to the subject a codon optimized nucleotide sequence that has at least 90% sequence identity over the full-length of SEQ ID NO: 5. Applicant further argues that references used, that is Chalberg and Fotin-Mleckzek together, do not disclose or suggest a sequence that is 90% identical to SEQ ID NO: 5 and a skilled artisan would not have engineered a nucleotide sequence to reach SEQ ID NO: 5. There are a myriad of techniques, algorithms, and services for optimizing a given sequence, including making manual changes to the coding sequences. Therefore, codon optimization is not merely a routine task but involves a complex and nuanced process that requires a deep understanding of the target organism.
In response, it is noted that codon optimization of RDH12 cDNA was known in the art as well as the amino acid sequence of SEQ ID NO: 2 was known in the art as disclosed by Chalberg and Fotin-Mleczek. Given that the amino acid sequence of the RDH12 protein was known in the art, an artisan would have been able to produce a number of nucleotide sequences that encoded the amino acid sequence of SEQ ID NO: 2 and one would have expected SEQ ID NO: 5 to have been one of such sequences, through routine optimization. There is no evidence, on the record, that SEQ ID NO: 5 had any unexpected properties. It is noted that applicant has not tested the activity of SEQ ID NO: 5.
The rejection is maintained.
Conclusion
No claims are 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.
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/D.T.Y./Examiner, Art Unit 1635
/RAM R SHUKLA/Supervisory Patent Examiner, Art Unit 1635
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