DETAILED ACTION
Applicant’s response filed August 17, 2025 has been received and entered into the application file. All arguments have been fully considered. Claims 1-7, 9 and 11-13 are currently pending. Claims 8 and 10 are cancelled. Claim 13 is new. Claims 1-2 are currently amended. Claims 4-7 and 9 were previously withdrawn as being drawn to nonelected Inventions Group 2 and Group 3, however claim 9 is currently indicated as “Original”. For purposes of compact prosecution, the amendment will not be considered non-compliant, but any future amendments which fail to comply with 37 C.F.R § 1.121 will receive a notice of non-compliant amendment.
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 .
OBJECTIONS/REJECTIONS WITHDRAWN
Drawings
The corrected drawing sheets submitted 8/17/2025 are in compliance with 37 CFR 1.121(d). The objection to the drawings is withdrawn.
Claim Objections
Applicant’s amendment filed 8/17/2025 has amended claim 2 to now spell out “Adeno-associated virus” thus obviating the previous objection to claim 2.
Claim Rejections - 35 USC § 112
RE: Rejection of Claim 2 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite:
Applicant’s amendment filed 8/17/2025 has amended claim 2 to recite the phrase "an AAV (Adeno-associated virus) vector". The amendment obviates the previous rejection of claim 2, therefore the rejection is withdrawn.
Claim Rejections - 35 USC § 102
RE: Rejection of Claim(s) 1-3 and 11-12 under 35 U.S.C. 102(a)(1) as being anticipated by Mao:
Applicant has amended claim 1 to now require the viral capsid protein mutant has one or more amino acid mutations selected from the group consisting of: Serine (S) at position 670 is mutated to alanine (A), and lysine (K) at position 534 is mutated to arginine (R). Claim 1 has been amended to remove the mutation directed to threonine (T) at position 251 is mutated to alanine (A).
It is noted that the cited reference to Mao taught constructing AAV-DJ vectors comprising viral capsid protein mutations wherein threonine (T) at position 251 is mutated to alanine (A) (Abstract: Background, Results and Conclusion; Construction of AAV-DJ mutants, page 2 of 8). Thus, Applicant’s amendment overcomes the previous rejection under 35 U.S.C. 102(a)(1) as being anticipated by Mao. Therefore, the rejection is withdrawn.
Claim Rejections - 35 USC § 103
RE: Rejection of claims 3 and 11-12 under 35 U.S.C. 103 as being unpatentable over Gabriel, as evidenced by US 2007/0243526, and further in view of Mao:
Applicant’s arguments (pages 5-8), filed 8/17/2025, with respect to the limitation directed to the AAV vector is an AAV-DJ vector, have been fully considered and are persuasive. Therefore, the rejection of claims 3 and 11-12 under 35 U.S.C. 103 as being unpatentable over Gabriel, as evidenced by US 2007/0243526, and further in view of Mao has been withdrawn.
REJECTIONS MAINTAINED
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.
Claim(s) 1-2 remain rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gabriel et al., (HUMAN GENE THERAPY METHODS 24: 80-93 (April 2013), previously cited) (“Gabriel”), as evidenced by US 2007/0243526 (previously cited) (“US ‘526”).
The rejection has been updated in view of Applicant’s amendment.
Gabriel teaches of bioengineering adeno-associated viral vector (AAV) capsid at specific serine (S), threonine (T) or lysine (K) residues in order to reduce destruction by host cellular kinase/ubiquitination/proteasomal machinery that targets the AAV capsid, thus resulting in improved transduction efficiency both in vitro and in vivo (Abstract and FIGs. 4B, 4D and 4F).
Regarding claim 1, Gabriel teaches constructing several mutant capsid constructs as follows:
15 S/T to alanine (A);
9 K to arginine (R); and
2 double K -> R vectors.
Gabriel’s FIG. 2 illustrates the locations of the various mutations, including mutation of T251, S668 and K532.
It is noted that FIG. 1 of US ‘526 evidences that Gabriel’s K532 correlates to the claimed K534 for AAV-DJ and Gabriel’s S668 correlates to the claimed S670 for AVV-DJ.
Thus, Gabriel’s teaching anticipates a viral capsid protein mutant wherein the viral capsid protein mutant has amino acid mutations wherein S668 (S670) is mutated to alanine (A) and K532 (K534) is mutated to arginine (R), wherein the mutated positions correspond to positions 670 and 534 of the sequence shown as SEQ ID NO:1, i.e. wild type AAV-DJ.
Regarding claim 2, and the limitation “wherein the viral capsid protein mutant has the activity of promoting an AAV (Adeno-associated virus) vector to infect inner ear supporting cells”, it is noted that Gabriel does not further comment on infecting inner ear supporting cells. However, although Gabriel does not state the mutant has the activity to infect inner ear supporting cells, the fact that Gabriel teaches the same mutation of serine (S) at position 670 is mutated to alanine (A), and lysine (K) at position 534 is mutated to arginine (R) as disclosed in the instant specification (pages 9, 22 and 24) means that any and all results of the AAV-DJ vector disclosed by Gabriel, whether recognized at the time of publication or not, were inherently achieved by the reference AAV vector. MPEP 2112.01
Response to Remarks:
Applicant has traversed the rejection of record on the grounds that the cited reference to Gabriel does not teach an AAV-DJ vector comprising a mutant with S670A or K534R, as discussed at Applicant’s remarks (page 9).
Applicant’s argument has been fully considered, but is not found persuasive since claims 1-2 as currently written do not require an AAV that is an AAV-DJ.
NEW GROUND(S) OF REJECTION, NECESSITATED BY AMENDMENT
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 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 13 is rejected under 35 U.S.C. 103 as being unpatentable over Gabriel et al., (HUMAN GENE THERAPY METHODS 24: 80-93 (April 2013), previously cited) (“Gabriel”), as evidenced by US 2007/0243526 (previously cited) (“US ‘526”), as applied to claims 1-2 above.
The teaching of Gabriel, as evidenced by US 2007/0243526 is set forth above.
Regarding claim 13, it is noted that Gabriel teaches of bioengineering adeno-associated viral vector (AAV) capsid at specific serine (S), threonine (T) or lysine (K) residues in order to reduce destruction by host cellular kinase/ubiquitination/proteasomal machinery that targets the AAV capsid, thus resulting in improved transduction efficiency both in vitro and in vivo (Abstract and FIGs. 4B, 4D and 4F).
Gabriel teaches constructing several mutant capsid constructs as follows:
15 S/T to alanine (A);
9 K to arginine (R); and
2 double K -> R vectors.
Gabriel’s FIG. 2 illustrates the locations of the various mutations, including mutation of T251, S668 and K532.
Gabriel’s Table 2 and FIGS. 4 and 5 teaches the mutant T251A. Gabriel differs from the instant invention in that Gabriel does not further exemplify the viral capsid protein mutant comprising the mutation T251A in combination with S668A or K532R.
However, Gabriel clearly teaches the disclosed mutations improve hepatic gene transfer (page 86, right col, last paragraph; FIG 5A-5B).
Therefore, it is submitted that because each of the types of serine (S), threonine (T) or lysine (K) mutations disclosed by Gabriel were known to individually promote improved gene transduction, it would further have been obvious to one having ordinary skill in the art to combine mutations for the purpose of producing an AAV vector that promotes improved gene transduction. Combination of multiple products (viral capsid protein mutations) each known to have the same effect to produce a final product having the same effect is prima facie obvious. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
The person of ordinary skill in the art would have been motivated to modify the AAV composition of Gabriel to include more than one capsid protein mutation, specifically the mutation T251A in combination with S668A or K532R for the predictable result of successfully promoting improved gene transduction, thus meeting the limitation of claim 13.
Thus, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Allowable Subject Matter
Claims 3 and 11-12 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.
Conclusion
No claim is 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.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to E. YVONNE PYLA whose telephone number is (571)270-7366. The examiner can normally be reached M-F 9am - 6pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, CHRISTOPHER BABIC can be reached at 571-272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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E. YVONNE PYLA
Primary Examiner
Art Unit 1633
/EVELYN Y PYLA/Primary Examiner, Art Unit 1633