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 .
Priority
This application is a national stage entry of 35 U.S.C. 371 of PCT/US2022/018986 (filed on 03/04/2022) and claims benefit of US provisional 63/156,766 (filed on 03/04/2021).
Election/Restrictions
Applicants’ election without traverse of species of SEQ ID NO: 3 filed on 06/04/2026 is acknowledged.
SEQ ID NO: 3 is a nucleic acid sequence that inhibits TLR9 activation (See, ¶0359 of Specification). While Applicants identified all of claims 1,4,8-9,12,14-17,20-22,25,33-34,36,38-39,46-49 as reading on the elected species, claims 17, 36, and 39 do not, in fact, read on the elected species (they are drawn to species which would activate TLR, which SEQ ID NO: 3 does not). As such, claims 17, 36 and 39 are withdrawn from consideration.
Claims Status
Claims 1,4,8-9,12,14-17,20-22,25,33-34,36,38-39,46-49 are pending
Claims 17, 36, and 39 are withdrawn per election of species.
Claims 1,4,8-9,12,14-16,20-22,25,33-34,38,46-49 have been examined on the merits.
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.
Claims 1,4,8,9,12,16,20,21,22,25,33,34,38,46,47,48,49 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chan et al (US 2019/0316151 A1; as cited in the IDS filed on 03/25/2024).
Chan et al discloses an invention of viral genomes modified to include nucleotide sequences that bind to TLR9 (See, Abstract).
Regarding claims 1 and 21, Chan et al discloses a self-complementary (sc) AAV vector with eGFP (scAAV-GFP) flanked by AAV2 inverted terminal repeats (ITRs) with cytomegalovirus (CMV) promoter, SV40 intron, SV40 polyA sequence that is engineered to have 3 copies of telomere (TTAGGG) inserted and separated by AAAAA linkers, resulting in scAAV-eGFP-3xtelomere. The 3x telomere were inserted between left ITR and CMV promoter to result in scAAV-3xtelomere-eGFP (See, ¶0128-0129). This reads on, a vector construct comprising (a) a polynucleotide comprising a promoter operably linked to a nucleic acid of interest, as the AAV is operably linked and we have a eGFP with CMV promoter, (b) a first terminal repeat and a second terminal repeat; and (c) a backbone polynucleotide comprising a nucleic acid sequence that modulates a Toll-like receptor (TLR), as the telomere sequence (TTAGG) prevents TLR-mediated inflammation, reduces proinflammatory cytokines, and increases transgene expression (See, ¶0108), of claim 1. This also reads on, a composition comprising a vector construct of claim 1, of claim 21.
Regarding claim 4, following the discussion above, the vector construct disclosed by Chan et al has 3 copies of the sequence. This reads on, wherein the backbone polynucleotide comprises between 2-500 copies of the nucleic acid sequence that modulates the TLR.
Regarding claim 8, following the discussion above, the vector construct disclosed by Chan et al has the nucleic acid sequence that modulates the TLR is positioned within 500 nucleotides of less from the first terminal repeat or the second terminal repeat.
Regarding claim 9, following the discussion above, Chan et al disclosed that SEQ ID NO: 6, (TTAGGG)4, is a short nucleotide sequence for inhibition of TLR9 (See, ¶0101). This reads on, wherein the TLR comprises TLR9.
Regarding claim 12, following the discussion above, Chan et al disclosed that telomere sequence used in the engineering of scAAV-3xtelomere-eGFP is SEQ ID NO: 9, which comprises SEQ ID NO: 6, is a TLR9 inhibitor and is a 100% sequence match for instant SEQ ID NO: 3 (See, Alignment in APPENDIX). This reads on, wherein the nucleic acid sequence that modulates the TLRR comprise a sequence SEQ ID NO: 3.
Regarding claim 16, following the discussion above, Chan et al discloses their results show that inclusion of human telomeric sequence SEQ ID NO: 6 in an AAV genome, prevents TLR-mediated inflammation, reduces pro-inflammatory cytokines, and increases transgene expression (See, ¶0108). This reads on, wherein the nucleic acid sequence that modulates the TLR is capable of inhibiting a TLR inflammatory response.
Regarding claim 20, following the discussion above, Chan et al disclosed that the ITRs are AAV2 (See, ¶0128-0129). This reads on, wherein the first terminal repeat and/or the second terminal repeat is an ITR from AAV2.
Regarding claims 22 and 25, following the discussion above, Chan et al further discloses the sc vectors were packaged into AAV2 by triple transfection of HEK293 cells and then purified with a final yield of 0.5-3 x 1013 vg (See, ¶0131). This reads on, a method for packaging the nucleic acids of interest and the nucleic acid sequence that modulates a TLR in an AAV capsid, comprising transfecting a cell in vitro with a vector construct…, one or more AAV packaging genes, wherein nucleic acid of interest and nucleic acid sequence that modulates the TLR are packaged in the AAV capsid of claim 22. This also reads on, an AAV particle produced by the method of claim 22, of claim 25, as Chan et al collected, purified, and quantified the AAV particles produced by the method.
Regarding claims 33 and 34, following the discussion above, Example 7 of Chan et al discloses that intravenous delivery of AAV of scAAV-eGFP-3xtelomere into the tail vein of mice showed little to no increase of inflammatory markers compared to controls and other vectors (See, ¶0122 and Figure 12). This reads on, a method of modulating an immune response in a subject, comprising administering to said subject an effective amount of the AAV particle of claim 25, of claim 33. This also reads on, wherein the nucleic acid sequence that modulates the TLR is capable of inhibiting a TLR inflammatory response, which reduces the subject’s immune response to the gene therapy comprising administration of the viral particle to the subject, of claim 34, as there was no increase in inflammatory markers.
Regarding claim 38, following the discussion above, Chan et al disclosed example 7 that AAV particle that is administered causes reduced inflammatory response in a host as compared to an AAV particle that does not contain the portion of a backbone comprising the nucleic acid sequence that modulates the TLR. Evidenced by figure 12 of Chan et al.
Regarding claim 46, following the discussion, Chan et al disclosed that telomere sequence used in the engineering of scAAV-3xtelomere-eGFP is SEQ ID NO: 9, which is the same as SEQ ID NO: 6, is a TLR9 inhibitor and is a 100% sequence match for instant SEQ ID NO: 3 (See, Alignment in APPENDIX). This reads on, wherein the nucleic acid sequence that modulates the TLR comprises… SEQ ID NO: 3.
Regarding claim 47, following the discussion above, Chan et al disclosed a vector construct with (TTAGGG)4 ,SEQ ID NO: 9, which is 4 repeats of instant SEQ ID NO: 55 in tandem, which is a 100% sequence match (See, Alignment in APPENDIX).
Regarding claims 48 and 49, following the discussion above, Chan et al disclosed a vector sequence with 3 copies of a TLR modulating nucleic acid sequence that is 100% sequence match for instant SEQ ID NO: 3 (See, Alignment in APPENDIX). This reads on, wherein the nucleic acid sequence that modulates TLR comprises the sequence of SEQ ID NO: 3, of claim 48. This also reads on, wherein the nucleic acid sequence that modulates TLR comprises between one and 500 copies of the sequence of SEQ ID NO: 3, of claim 49.
Therefore, claims 1,4,8-9,12,16,20-22,25,33-34,38,46-49 are anticipated by Chan et al.
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.
Claims 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Chan et al (US 2019/0316151 A1; as cited in the IDS filed on 03/25/2024).
The teachings of Chan et al are set forth above.
Regarding claim 14, following the discussion above, Chan et al discloses viral vectors with their own protection against host immune and inflammatory systems, such as short nucleic acid sequences that inhibit activation of TLR9. The nucleic acid sequence SEQ ID NO: 6 (TTAGGG)4 (TTAGGG repeated 4 times) is an inhibitory sequence that multiple copies can be included in the nucleic acid sequence in tandem or in a viral vector with spacer or linker sequences or other portions of the viral genome. Chan et al discloses that one to 20 copies can be used and they can be on the plus or minus strand of the viral genome (See, ¶0100-0101).
Chan et al a vector construct but is silent about the length of the polynucleotide backbone sequence that modulates a TLR.
However, the length of the backbone is considered to be prima facie obvious, as the instant claim requires between 4000-8000 or 5000-7000 nucleotides in length. One of ordinary skill in the art would be able to include as many copies and linkers to make the length of the backbone be between 4000-8000 or 5000-7000 nucleotides in length. As such, the length of the backbone for the limitation would have been a matter of routine optimization (See, MPEP 2144.05).
Regarding claim 15, following the discussion above, Chan et al does not disclose the percentage of the total nucleic acid sequence of the backbone polynucleotide is the nucleic acid sequence that modulates the TLR.
However, the percentage of the nucleic acid sequence of the backbone that is the TLR is considered to be prima facie obvious, as the instant claim requires 0.5% to 10% and Chan et al provides nucleic acid sequence and provides motivation to include up to 20 copies with linkers to provide more efficacy. One of ordinary skill in the art would be able to include as many copies and linkers to make the length desired and calculate the percentage such that the percentage of the backbone sequence that comprises the nucleic acid sequence that modulates the TLR is between 0.5% to 10%. As such, the percentage of the backbone for the limitation would have been a matter of routine optimization (See, MPEP 2144.05).
Therefore, claims 14 and 15 are rendered obvious over Chan et al.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Caroline M Lara whose telephone number is (571)272-4262. The examiner can normally be reached 7:00 to 4:30pm M-Th.
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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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/CAROLINE M LARA/Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633
APPENDIX
SEQUENCE ALIGNMENT
RE: Claims 12 and 46
Query (Qy), SEQ ID NO: 3 vs Database(Db) US 2019/0316151 A1 SEQ ID NO: 6
(App # 16/167,764)
PNG
media_image1.png
194
621
media_image1.png
Greyscale
RE: Claims 12 and 46
Query (Qy), SEQ ID NO: 3 vs Database(Db) US 2019/0316151 A1 SEQ ID NO: 9
(App # 16/167,764)
PNG
media_image2.png
198
618
media_image2.png
Greyscale
RE: Claim 47
Query (Qy), SEQ ID NO: 55 vs Database(Db) US 2019/0316151 A1 SEQ ID NO: 9
(App # 16/167,764)
PNG
media_image3.png
200
617
media_image3.png
Greyscale
Prosecution Insights