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 .
Status of Application/Amendments/Claims
Applicant’s response filed on 6/22/2026 has been considered. Claims 8-16, 44 and 47-52 are canceled. Claims 1-7 and 22 are pending. Claim 22 is withdrawn without traverse from further consideration pursuant to 37 CFR 1.142 (b) as being drawn to a nonelected invention, there being no allowable generic or linking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. Claims 1-7 are the subject of the present Official action. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Priority
Applicant’s claim for the benefit of a prior-filed application PRO 63/155,624 and 371 of PCT/US2022/018543 filed on 3/2/2021 and 3/2/2022, respectively, under 35 U.S.C 119(e) or under 35 U.S.C 120, 121 or 365(c) is acknowledged.
Accordingly, the effective priority date of the instant application is granted as 3/2/2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 6/22/2026 were received. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement was considered by the examiner.
Withdrawn Claim Rejections in response to Applicant’s arguments or amendments
The duplicate claims warning with respect to claims 1 and 6 has been withdrawn in light of applicant’s amendments to claim 1.
The 35 U.S.C. 112(b) rejection of claim 4 has been withdrawn considering applicant’s arguments and amendments to claim 1.
The 35 U.S.C. 102(a)(2) rejection of claims 1-4 and 6-7 as being anticipated by Sabin et al. US 2022/0241430 and 35 U.S.C. 103 rejection of claims 1-7 over Sabin in view of Guenther et al. Molecular Therapy 27.3 (2019) has been withdrawn in light of applicant’s amendments.
New Claim Rejections - 35 USC § 112a, Written Description
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 1-7 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 for introducing new matter. This rejection is supported by Bennett et al. "Understanding capsid assembly and genome packaging for adeno-associated viruses." Future virology 12.6 (2017): 283-297 (hereinafter Bennett). This rejection is newly applied to address applicants claim amendments filed on 6/22/2026.
Claim 1 describes an AAV comprising VP1, VP2 and VP3 polypeptides wherein said VP3 polypeptide comprises a heterologous amino acid segment having the ability to bind to a binding partner, wherein the VP1 and VP2 polypeptides lack said heterologous amino acid segment. However, VP1, VP2 and VP3 AAV capsid proteins display a nested structural relationship, whereby the VP3 polypeptide is entirely contained within the VP2 polypeptide and the VP2 polypeptide is entirely contained within the VP1 polypeptide (see pg 5 of Applicant’s remarks).
The claims are broadly interpreted as encompassing VP1 and VP2 polypeptides that “lack said heterologous amino acid segment”. Since the amino acid sequence of VP3 constitutes the entirety of the C-terminal domain for all three capsid proteins, any standard genetic insertion made within the VP3 region automatically alters VP1, VP2 and VP3 simultaneously. Thus, there is not a structure/function correlation for the genus of VP1 polypeptides and the VP2 polypeptides that lack said heterologous amino acid segment that are comprised within the same AAV comprising the VP3 having the heterologous aa segment.
For each claim drawn to a genus, the written description requirement may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant identifying characteristics, i.e. structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in procession of the claimed genius. If a representative number of adequately descried species are not disclosed for a genus, the claim to that genus must be rejected as lacking adequate written description under 35 U.S.C. 112, para. 1.
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The applicant is on record stating that support for the amended claims is found in Figure 3. (see page 4 of Applicants’ remarks”). However, Figure 3 illustrates 2 AAV trans vectors comprising :1) AAV2 comprising a wild-type VP3 polypeptide and no VP1 polypeptides and no VP2 polypeptides (VP1/2 Stop) (e.g, mutated VP1 start codon and stop codon in VP2) and 2) AAV2 that contains wild-type VP1 and VP2 polypeptides and no VP3 polypeptides (VP1/2 (VP3 STOP) (Isoleucine mutation) (see paragraph 0025 of the published application). Figure 6 is a table of the AAV titers produced using the indicated combination of AAV vectors having titers within the ranges of greater than 1x1011 to 1x1012. All these examples comprise viruses packaged using combinations of the mutated VP1/2 Stop and VP3 STOP of both AAV2 trans. This disclosure is not deemed to be descriptive of the complete structure of a representative number of species encompassed by the claims as one of skill in the art cannot envision all the VP1 polypeptides and the VP2 polypeptides of said AAV lacking said heterologous amino acid segment based on the teachings in the specification.
The instant specification provides no other examples to support amending claim 1 to describe an AAV comprising VP1, VP2 and VP3 polypeptides wherein said VP3 polypeptide comprises a heterologous amino acid segment having the ability to bind to a binding partner, wherein the VP1 and VP2 polypeptides lack said heterologous amino acid segment. Although the specification does describe that chimeric viruses may be constructed by combining the mutated VP1/2 STOP and the VP3 STOP of both AAV2, it does not isolate the tag to the VP3 isoform exclusively while preserving native, tag-free VP1 and VP2 on the same exact physical vector. Furthermore, Fig 3 and Pg 11 lines 4-7 of the specification do not describe an AAV vector with a modified VP3 alongside untagged VP1 and VP2 but rather show inter-viral vector linking and mosaic capsid mixing.
The prior art shows that the VP3 sequence is entirely nested within the sequences of VP1 and VP2 as shown by Bennett (Bennett, Methods-Capsid assembly pg 3). The practitioner in the art would readily understand that VP1, VP2 and VP3 AAV capsid proteins display a nested structural relationship, whereby the VP3 polypeptide is entirely contained within the VP2 polypeptide and the VP2 polypeptide is entirely contained within the VP1 polypeptide, and all three VPs are translated from one mRNA.
Given the breadth of AAV where the VP3 polypeptide comprises a heterologous amino acid segment and the VP1 polypeptides and the VP2 polypeptides lack said heterologous amino acid segment, wherein all three VPs are translated from one mRNA, the instant specification does not provide sufficient written description to support the claimed genus of constructs comprising overlapping nucleotide sequences of capsid proteins: VP1, VP2 and VP3, wherein said VP3 polypeptide comprises a heterologous amino acid segment having the ability to bind to a binding partner, wherein the VP1 and VP2 polypeptides lack said heterologous amino acid segment. Therefore, the specification does not describe the claimed AAV in such full, clear, concise and exact terms so as to indicate that Applicant has possession of these AAVs at the time of filing the present application. Thus, the written description requirement has not been satisfied.
Claim Rejections - 35 USC§ 112, Scope of Enablement
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 1-7 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for an AAV2 comprising VP1, VP2 an VP3 polypeptides, wherein said VP3 polypeptide comprises a heterologous amino acid segment at an amino acid position within three amino acid residues of an amino acid residue corresponding to position 53 or position 588 of a reference VP1 polypeptide having the amino acid sequence set forth in SEQ ID NO: 2 having the ability to bind to a binding partner, wherein the AAV2 encodes a wild-type VP3 polypeptide and wherein the start codon of the VP1 polypeptide is deleted and a stop codon is inserted into the coding frame of the VP2 sequence between the VP2 start codon and the VP3 start codon (e.g, mutated VP1 start codon and stop codon in VP2) so no VP1 polypeptides and no VP2 polypeptides are produced, does not reasonably provide enablement for an AAV construct comprising overlapping nucleotide sequences of capsid proteins: VP1, VP2 and VP3, wherein said VP3 polypeptide comprises a heterologous amino acid segment having the ability to bind to a binding partner, wherein the VP1 and VP2 polypeptides lack said heterologous amino acid segment. This rejection is supported by Bennett et al. "Understanding capsid assembly and genome packaging for adeno-associated viruses." Future virology 12.6 (2017): 283-297 (hereinafter Bennett). This rejection is newly applied to address applicants claim amendments filed on 6/22/2026.
The factors listed below have been considered in the analysis of enablement:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The breadth of claims read on an AAV composition encompassing VP1 and VP2 polypeptides that “lack said heterologous amino acid segment”. Since the amino acid sequence of VP3 constitutes the entirety of the C-terminal domain for all three capsid proteins, any standard genetic insertion made within the VP3 region automatically alters VP1 and VP3 simultaneously. This is in stark contrast to the applicant’s specification, wherein examples are provided supporting chimeric viruses that may be constructed by combining the mutated VP1/2 STOP and the VP3 STOP of both AAV2, however, it does not isolate the tag to the VP3 isoform exclusively while preserving native, tag-free VP1 and VP2 on the same exact physical vector. Furthermore, Fig 3 and Pg 11 lines 4-7 of the specification do not describe an AAV vector with a modified VP3 alongside untagged VP1 and VP2 but rather show inter-viral vector linking and mosaic capsid mixing.
The state of the prior art shows that the VP3 sequence is entirely nested within the sequences of VP1 and VP2 as shown by Bennett (Bennett, Methods-Capsid assembly). The practitioner in the art would readily understand that VP1, VP2 and VP3 AAV capsid proteins display a nested structural relationship, whereby the VP3 polypeptide is entirely contained within the VP2 polypeptide and the VP2 polypeptide is entirely contained within the VP1 polypeptide, and all three VPs are translated from one mRNA.
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The instant specification provides enabling embodiments to chimeric viruses may be constructed by combining the mutated VP1/2 STOP and the VP3 STOP of both AAV2, it does not isolate the tag to the VP3 isoform exclusively while preserving native, tag-free VP1 and VP2 on the same exact physical vector. Furthermore, Applicant is on record stating that support for the amended claims is found in Figure 3. (see page 4 of Applicants’ remarks”). However, Figure 3 illustrates 2 AAV trans vectors comprising :1) AAV2 comprising a wild-type VP3 polypeptide and no VP1 polypeptides and no VP2 polypeptides (VP1/2 Stop) (e.g, mutated VP1 start codon and stop codon in VP2) and 2) AAV2 that contains wild-type VP1 and VP2 polypeptides and no VP3 polypeptides (VP1/2 (VP3 STOP) (Isoleucine mutation) (see paragraph 0025 of the published application). Figure 6 is a table of the AAV titers produced using the indicated combination of AAV vectors having titers within the ranges of greater than 1x1011 to 1x1012. All these examples comprise viruses packaged using combinations of the mutated VP1/2 Stop and VP3 STOP of both AAV2 trans. Additionally, the Specification discloses that to produce a VP3 polypeptide having a heterologous amino acid segment “the start codon of the VP1 sequence can be changed from ATG to ATC, CTT, or TCT. In addition, the stop codon inserted into the coding frame of the VP2 sequence between the VP2 start codon and the VP3 start codon can be any appropriate stop codon (e.g., TAA, TGA, or TAG), and the stop codon can be inserted at any appropriate location between the VP2 start codon and the VP3 start codon. For example, a stop codon can be inserted between 138 and 202 codons before the VP3 start codon.” (para [0116] of the published application).
Thus, applicant is not enabled for an AAV construct comprising overlapping nucleotide sequences of capsid proteins: VP1, VP2 and VP3, wherein said VP3 polypeptide comprises a heterologous amino acid segment having the ability to bind to a binding partner, wherein the VP1 and VP2 polypeptides lack said heterologous amino acid segment which would lead one of ordinary skill in the art to practice the claimed invention without undue experimentation.
Conclusion
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 extension fee 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDER NICOL whose telephone number is (571)272-6383. The examiner can normally be reached on M-F 8-5 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria Leavitt can be reached on (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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Alexander Nicol
Patent Examiner
Art Unit 1634
/ALEXANDER W NICOL/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
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