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 II, claims 44-47, 51, and 67, and the species of a targeting peptide having the amino acid sequence of SEQ ID NO: 1, where the modified AAV capsid protein is derived from an AAV1 capsid protein, where the targeting peptide is inserted after residue 590 of the AAV1 capsid protein of SEQ ID NO: 164 (i.e., in positions 594-600 of SEQ ID NO: 167), in the reply filed on 06/02/2026 is acknowledged.
Claims 1,3-4,7-8,13,18, 24-27, 30, and 61 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 06/02/2026 .
Claims 44-47, 51, and 67 are currently under examination.
Priority
Applicant’s claim for the benefit of a prior-filed application provisional application 63180394 , filed on 04/27/2021 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) submitted 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.
Drawings
The drawings are objected to because Figures. 6, 8, and 10 are blurry, such that the structural features relationship depicted therein cannot readily ascertained. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 112
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 47 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.
Regarding claim 47, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
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.
Claim 45 is 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.
Claim 44, recites “ modified adeno-associated virus (AA V) comprising a
therapeutic transgene operably linked to a cochlea-specific promoter, wherein the modified AAV comprises a modified capsid protein, wherein the modified capsid protein comprises a targeting peptide having a sequence selected from any one of the sequences of SEQ ID NOs: 1-155”. Claim 45 depends from claim 44 and further requires that the modified capsid comprises a therapeutic transgene for treating or preventing a hearing or vestibular disorder. The specification, however, does not reasonably convey to a person of ordinary skill in the art that the inventors was in possession of the claimed modified capsids having this combination of features.
The instant specification provides disclosure of AAV1-, AAV2-, and AAV9- derived capsids and their respective insertion positions. For example, the specification states a targeting peptide may be inserted after residue 590 of AAV1, residue 587 of AAV2, or residue 588 of AAV9. The specification further identifies AAV1 targeting peptides as SEQ ID NOs. 1-44,150, and 154, AAV2 targeting peptides as SEQ ID NO.152,154 and 45-100, and AAV9 targeting peptides as SEQ ID NOs.101-149, 153, and 155. For example, example 1 describes generation of peptide-modified AAV libraries by inserting random peptides into AAV1,AAV2, and AAV9 at positions 590,587, and 588, respectively, wherein the AAV1 library was subjected to rounds of in vivo enrichment, and sequencing was used to identify capsids variants. The specification expressly characterized the results as an assortment of enriched capsid variants, for which small library and fluorescent-based validation was ongoing. ( See Example 1). Thus, the specification provides evidence concerning the incorporation of the disclosed targeted peptide into certain AAV capsid serotypes. However, the disclosure does not provide a corresponding example, species, or other sufficiently detailed description of a modified capsid comprising both (1) one of the claimed targeting peptides (2) a therapeutic transgene for treating or preventing a vestibular or hearing disorder. Specifically, the specification does not demonstrate that any of the disclosed targeting peptide/AAV capsid combinations were constructed with a therapeutic transgene and successfully delivered the therapeutic transgene to vestibula, nor does it demonstrate that when the disclosed targeting peptides is incorporated into the disclosed AAV capsids and further combined with a therapeutic transgene, would retain the requisite targeting properties and are capable of specifically delivering the therapeutic transgene to vestibular tissue so as to necessarily and predictably achieve a real-world, clinically meaningful, therapeutic result(s) of treating or preventing all hearing or vestibular disorders, as required by the dependent claims. In other words, the disclosure of the AAV1, AAV2,AAV9 capsid bearing the disclosed targeting sequence does not adequately describe the additional claimed combination of such modified capsid with a therapeutic transgene for treatment or prevention of any hearing or vestibular disorders, nor does it establish the structure-function correlation demonstrating that the disclosed combination would specifically deliver such therapeutic transgene to the vestibular tissue.
Therefore, the claimed subject matter encompass a combination for which the specification does not disclose a representative number of species or sufficient characteristic demonstrating possession of the claimed genus. This is particularly significant because the claimed subject matter encompasses numerous combinations of targeting peptide, AAV capsid serotype, insertion site, and therapeutic transgene together with the functional requirement of delivery to vestibular tissue and providing the desired therapeutic benefit. In other words, the disclosure of particular modified capsids in particular AAV serotype does not, by itself, establish possession of the broader claimed combination including any therapeutic transgene to treat or prevent any vestibular or hearing disorders.
According to the MPEP, when the claims are directed to a broad genus, the written description may be satisfied by disclosure of a representative number of species, or by identifying characteristics sufficient to demonstrate possession of the claimed genus. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc
To conclude, the specification does not 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 entire genus recited in claim 45.Therefore, claim 45 lacks adequate written description support under 35 U.S.C 112(a).
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 (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 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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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 44-47, 51 and 67 are rejected under 35 U.S.C. 103 as being unpatentable over Bartolome et al ( US 2021/0095313 A1), in view of McGovern et al ( US 2020/0370137 A1) and Dumas et al (WO 99/53051).
Regarding claim 44-47, 51 and 67, Bartolome et al disclose an AAV vector for treatment and prevention of genetic hearing loss. [0037]. Bartolome et al teach delivery of rAAV vectors to cells of the inner ear and expressly describe vectors comprising therapeutic nucleic acid , including GJB2, operably linked to promoters suitable for cochlear support-cell expression. ( [0011], [0013]). Bartolome et al further identify the endogenous GJB2 promoter as a support-cell-specific promoter. [0172]. Bartolome et al additionally disclose that the rAAV expression vector may comprise a protein capsid variant optimally suited for cochlear delivery and expressly identify AAV1 among the AAV serotypes contemplated for rAAV vector. ( See claim 35, [0021], [0022]). Thus, Bartolome et al teach the claimed rAAV, a therapeutic transgene for treating genetic hearing loss, and a cochlear/support-cell specific promoter, as well as the use of engineered AAV capsid for cochlear delivery.
It is submitted that Bartolome et al do not expressly teach the claimed modified capsid protein comprising the particular targeting peptide of the elected species (i.e. SEQ ID.NO.1).
McGovern et al disclose a method of engineering AAV capsids by inserting peptide sequences into capsid proteins to provide modified AAV variants having desired targeting/tropism characteristics. McGovern et al further teach that the modified capsids would be useful for the delivery of genome engineering molecules and gene therapy molecules for the treatment of a subject in need thereof. ( See abstract, and [0126]). McGovern expressly teach insertion of peptides into AAV capsid at defined positions. Of particular relevance, McGovern expressly teach that when the capsid protein corresponds to AAV1, a peptide may be inserted at amino acid position of 590. ([0056] and [0060]). McGovern therefore teaches the structural limitation of an AAV1 capsid having an inserted targeting peptide at residue 590. McGovern et al also teach that the engineered AAV vectors may be used in pharmaceutical compositions and that peptide sequences can be incorporated into AAV capsids to alter the characteristic/tropism of the resulting vector. ([0072]). However, McGovern et al do not teach the specific targeting peptide of the selected species, for example, SEQ ID.NO.1.
Dumas et al supplement Bartolome et al and McGovern by teaching expressed sequence tags (EST) sequences corresponding to human secreted proteins and the corresponding EST-related polypeptides. Of particular relevance, Dumas et al disclose SEQ ID NO 1458 comprising of 24 amino acids peptide having the sequence MVISAGALLWMAWDGQLSRPEGAR, which includes, SPREGAR, the sequence corresponding to Applicants elected SEQ ID NO.1. Dumas et al further contemplate expression vectors designed for gene therapy including viral and retroviral vectors and teach the use of EST-related sequences and portions thereof to express proteins or polypeptide in host organisms to produce beneficial effect. ( See abstract, and page 10- lines 10-13 and lines 23-26). Thus, Duma et al provide both a known peptide sequence containing specific SRPEGAR sequence of the elected species and contemplate the possibility of incorporating and use of peptide/signal sequences in therapeutic vector and fusion protein context.
Therefore, it would have been prima facie obvious for one with ordinary skill in the art at the time the invention was filed to modify the vector of Bartolome et al according to the teachings of McGovern et al by incorporating a peptide at the disclosed residue 590, and select the SRPEGAR containing peptide disclosed by Dumas et al. A person of ordinary skill in the art would have had a reasonable expectation of success because McGovern et al teach that peptide insertion into AAV capsid can be used to later targeting/tropism, specifically including peptide insertion into an AAV1 capsid at residue 590. Dumas et al independently teach that the elected peptide-containing sequences were known and usable in therapeutic vector and fusion protein context. The modification, therefore, does not require the discovery of a new mechanism, but rather application of known peptide and capsid engineering teachings to the therapeutic AAV platform of Bartolome. In other words, instant claims are combining prior art elements according to known methods to yield predictable results. See MPEP 2143 (I)(A).
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FATIMAH KHALAF MATALKAH whose telephone number is (703)756-5652. The examiner can normally be reached Monday-Friday,7:30 am-4:30 pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Tracy Vivlemore can be reached on 571-272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/FATIMAH KHALAF MATALKAH/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
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