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 I (Claims 1-20 and 23-30; drawn to a method of linking two or more viral vectors) in the reply filed on January 24, 2025, is acknowledged.
Applicant further elected the following species:
a. A method of linking two or more viral vectors (Species A1; claims 1-20)
b. Species A1A (claims 3-5 and 7-14)
Furthermore, Applicant provisionally elected SPAAC as the reaction for covalent linkage in a telephonic interview with their representative, Ina Agaj, on January 31, 2025.
Claims 12-14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on January 24, 2025.
DETAILED ACTION
The amended claims filed on February 6, 2025, have been acknowledged. Claims 6 and 15-30 were cancelled. Claim 1 was amended. Claims 12-14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Claims 1-5 and 7-11 are pending and examined on the merits.
Rejections and/or objections not reiterated from the previous office action mailed November 6, 2025, are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application.
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
The applicant claims domestic priority from U.S. provisional application No. 63/584,196, filed on September 21, 2023. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Claims 1-5 and 7-11 receive domestic benefit from U.S. provisional application No. 63/584,196, filed on September 21, 2023.
New 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.
(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 1-5 and 7 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by United States Patent Application No. 20200224219 (Buning). This Is a new rejection necessitated by Applicant’s amendment to claim 1. Applicant’s traversal has been fully considered but is moot in response to the new rejection.
Regarding claim 1, Buning teaches a method of linking two or more viral vectors wherein a purified non-infective viral vector (for example, Cys2ΔHSPG) is bound to a column. Then, Dibenzylcyclooctyne-PEG4 -Maleimide linker (first surface moiety) is added to the column for 3 hours and functionalizes with the non-infectious viral vector. After a wash step, azide-modified molecules (such as an azide functionalized (second surface moiety) infectious AAV vector; Buning teaches that the term "targeting molecule" refers to a molecule allowing targeting of AAV particles to target cells. Buning teaches that the infectious AAV particle allows transport of the non-infectious particle into the target cell, thus, increasing the capacity of DNA to be introduced into said cell. As such, the infectious AAV particle would be a targeting molecule) were added and incubated for 72 hours. After a final wash step, coupled vectors were eluted (paragraphs 0041, 0084, and 0121-0122). As can be seen on page 6, the azide and DBCO react to form a covalent linkage.
Regarding the nucleic acid constructs, Buning teaches a composition of an infectious AAV particle according to the present invention with an at least one non-infectious AAV particle enables trans-splicing technology or two component systems (i.e. connection of two or more vector genomes through a cellular splice event enlarging thereby the coding capacity of AAV vectors) to be used for transduction of target cells ex vivo or in vivo. The infectious particle coupled to a non-infectious particle, e.g. so-called receptor blinded particles as a complex, will guide the complex towards the cell and mediate cell infection of the whole complex including the non-infectious particles. Thus, this technique allows to overcome the limited capacity of AAV vectors enabling the transduction of cells with a dual vector system, thereby increasing the capacity of components introduced into the cells. Thus, it is possible to enable trans-splicing or two component systems in vivo.
That is, the infectious AAV particle allows to transport the non-infectious particle into the target cell, thus, increasing the capacity of DNA to be introduced into said cell accordingly.
Further, the present invention relates to the use of the AAV particle according to the present invention, as a medicament for gene therapy (paragraphs 0063-0084).
Regarding claim 2, Buning teaches that their viral vectors were AAV2 viral vectors (paragraphs 0130-0131).
Regarding claims 3-5, Buning, as stated supra, teaches that they used a Dibenzylcyclooctyne (DBCO)-PEG4-Maleimide linker (first surface moiety) and azide linker (second surface moiety) for the covalent linkage reaction (this is a known SPAAC reaction).
Regarding claim 7, Buning, as stated supra, teaches on page 6 that the DBCO and azide reaction forms this linking structure between the first and second AAV vectors.
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.
Claims 1-2 and 8-11 are rejected under 35 U.S.C. 103 as being unpatentable over United States Patent Application No. 20200224219 (Buning) as applied to claims 1-2 above, and further in view of Nguyen et al. (International Journal of Pharmaceutics 605:1-19. 2021). This Is a new rejection made in response to Applicant’s amendment to claim 1. Applicant’s traversal has been fully considered but is moot in response to the new rejection.
The teachings of Buning are as discussed above.
Although Buning discloses the use of NHS ester for crosslinking antibodies [0118], Buning does not teach wherein NHS esters are used as part of the linking structure between the AAV capsid.
Nguyen teaches that click chemistry refers to the formation of a stable triazole linkage by the reaction between alkyne and azide groups. To do so, a linker is normally used for connecting molecules. In most cases, the functionalization of molecules with azide or alkyne moieties goes through carbodiimide or maleimide conjugation. Therefore, NHS esters or maleimide groups needs to be present on one side of the linker, while azide or alkyne groups must be located on the other side. Furthermore, Nguyen references Kotagiri which specifically teaches using NHS-PEG-DBCO and NHS-PEG-Azide for conjugating different molecules (page 11, paragraphs 3-4).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted maleimide of Buning with an NHS ester, as identified by Nguyen, to arrive at the instantly claimed invention. One of ordinary skill in the art would have a reason to substitute with a reasonable expectation of success because Nguyen teaches that it was well understood in the art that maleimide or NHS esters are used for click chemistry (such as SPAAC) as part of the linker structure. Furthermore, Nguyen teaches that Kotagiri successfully reduced to practice that NHS-PEG-DBCO and NHS-PEG-Azide linkers could be used to couple different molecules. Furthermore, Bunning teaches that there were at least 12 different serotypes of AAV known in the art [0042], and the cysteine based chemistry of Bunning would have required cysteine substitution of each and every AAV capsid to be crosslinked, while the NHS/amine based chemistry of Nguyen would have allowed the use of wild type AAV capsids across the different serotypes without the need for cysteine modification. Thus, the omission of the cysteine modification step would have been obvious to one having ordinary skill in the art at the time the invention was filed since it has been held that omission of an element and its function is obvious if the function of the element is no longer needed (see MPEP 2144.04 (II)). Therefore, it would have been obvious to one of ordinary skill in the art that NHS esters could have been used as part of the linking structure instead of maleimide with a reasonable expectation of success. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
Regarding claims 8 and 9, the specification discloses that NHS esters are capable of attaching to amine groups on a capsid protein (paragraph 0060).
Regarding claims 10-11, replacing the maleimide would result in a linking structure of NHS-PEG4-DBCO ester.
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 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KEENAN A BATES whose telephone number is (571)270-0727. The examiner can normally be reached M-F 7:30-5:00.
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, Doug Schultz can be reached on (571) 272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KEENAN A BATES/Examiner, Art Unit 1631
/JAMES D SCHULTZ/Supervisory Patent Examiner, Art Unit 1631