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 .
DETAILED ACTION
This Office Action is a response to Applicant’s Amendment and Remarks filed June 3, 2026.
Claims 4, 11 and 14 have been canceled. New claim 19 is acknowledged. Claims 1 and 6 have been amended.
Claims 1-3, 5-10, 12-13 and 15-19 are pending in the present application.
This application contains claims 16-18 drawn to an invention nonelected without traverse in the reply filed January 27, 2026. A complete reply to the final rejection must include cancellation of nonelected claims or other appropriate action (37 CFR 1.144). See MPEP § 821.01.
Accordingly, claims 1-3, 5-10, 12-13, 15 and 19 have been examined on the merits as detailed below:
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Rejections - 35 USC § 112
In the previous Office Action mailed March 3, 2026, claim 6 was 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 pre-AIA the applicant regards as the invention. This rejection is withdrawn in view of Applicant’s Amendment to the claim filed June 3, 2026.
Claim Rejections - 35 USC § 103
In the previous Office Action mailed March 3, 2026, claims 1-15 were rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent No. 12054714 B2 (SIRNAOMICS, INC.) in view of U.S. Patent No. 8273869 B2 (Alnylam Pharmaceuticals Inc.). This rejection is moot against claims 4, 11 and 14 in view of Applicant’s Amendment filed June 3, 2026 to cancel these claims. This rejection is maintained against the remaining claims for the reasons of record set forth in the previous Office Action mailed March 3, 2026. NOTE: New claim 19 is drawn to subject matter within the scope of the rejected claims and would have been rejected in the prior Office Action. Therefore, the instant rejection applies to new claim 19 as well.
Response to Arguments
In response to this rejection, Applicants traverse and argue that the Examiner relies on a single siRNA duplex described in Alnylam in support of the contention that it would have been obvious to combine this duplex with the PDoV constructs recited in the claims. Applicants submit that nothing in Alnylam teaches or suggests any of the siRNA molecules now recited in the amended claims, nor do any of the cited references, alone or in combination teach or suggest the combinations of siRNA molecules and PDoV moieties now recited in the instant claims. Applicants request withdrawal of the rejection.
Applicant’s traversal has been fully considered, however it is not found to be persuasive because contrary to Applicant’s argument, Alnylam does indeed teach and suggests a siRNA molecule as now recited in the amended claims. For example, Alnylam teach a particular siRNA nucleic acid which comprises SEQ ID NO: 22 of the present invention.
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NOTE: Regarding SEQ ID NO: 25 of the present invention, Alnylam teach the dsRNA of their invention comprise different backbone chemistries, including alternating 2'-O-methyl and 2'-fluoro modified nucleotides, for example.
It is maintained that before the effective filing date of the claimed invention, a chemical construct comprising a Peptide Docking Vehicle (PDoV) covalently linked to (a) a targeting moiety, and (b) a therapeutic nucleic acid, wherein the therapeutic molecule is an siRNA, and wherein the PDoV comprises multiple repeating units of histidine and lysine was known and taught in the prior art of SIRNAOMICS.
It would have been obvious and one of skill in the art would have been motivated to modify the teachings of SIRNAOMICS to include a PCSK9 siRNA comprising SEQ ID NO: 25 of the present invention since SIRNAOMICS taught a peptide docking vehicle for targeted nucleic acid delivery and Alnylam taught the desire to use gene therapy to target PCSK9 gene and protein expression.
Therefore, the subject matter of claims 1-3, 5-10, 12-13, 15 and 19 is obvious over SIRNAOMICS in view Alnylam.
Markush Rejection
In the previous Office Action mailed March 3, 2026, claims 4 and 11 were rejected on the judicially-created basis that it contains an improper Markush grouping of alternatives. This rejection is moot in view of Applicant’s Amendment filed June 3, 2026 to cancel these claims.
Non-Statutory Double Patenting
In the previous Office Action mailed March 3, 2026, claims 1-15 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 12054714 B2 (hereinafter, “’714 Patent”) in view of U.S. Patent No. 8273869 B2 (Alnylam Pharmaceuticals Inc.). This rejection is moot against claims 4, 11 and 14 in view of Applicant’s Amendment filed June 3, 2026 to cancel these claims. This rejection is maintained against the remaining claims for the reasons of record set forth in the previous Office Action mailed March 3, 2026. NOTE: New claim 19 is drawn to subject matter within the scope of the rejected claims and would have been rejected in the prior Office Action. Therefore, the instant rejection applies to new claim 19 as well.
Response to Arguments
In response to this rejection, Applicants traverse and argue that the rejection is based on the same rationale as the obviousness rejection discussed above and, for the same reasons as discussed above, no prima facie case of obviousness exists and withdrawal of the rejection respectfully is requested.
Applicant’s traversal has been fully considered, however it is not found to be persuasive because it is maintained that although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims embrace and encompass claims 1-12 of the ‘714 Patent.
The claims of the present invention are drawn to a chemical construct comprising a Peptide Docking Vehicle (PDoV) covalently linked to (a) a targeting moiety, and (b) a therapeutic nucleic acid, wherein said therapeutic nucleic acid inhibits expression of PCSK9 gene, wherein said therapeutic nucleic acid is an siRNA duplex, having 16-24 contiguous base pairs and an antisense strand comprising a sequence selected from the group consisting of SEQ ID NO:13. 15-21, 23-42 and 73-87, and wherein the PDoV comprises multiple repeating units of histidine and lysine.
The claims of the ‘714 Patent are drawn to a chemical construct comprising a peptide construct covalently linked to: (a) a targeting ligand; and (b) a first therapeutic oligonucleotide; and, optionally (c) a second therapeutic oligonucleotide that may be the same or different than the first, wherein the amino acid sequence of said peptide construct is selected from the group consisting of: KHHHCKH (SEQ ID NO: 3); HKHHHCKH (SEQ ID NO: 4); HHKHHHCKH (SEQ ID NO: 5); HHHKHHHKCHHHKHHH (SEQ ID NO: 6); HHHKHHCKHHH (SEQ ID NO: 7); HHHKHHCRHHH (SEQ ID NO: 8); HKHHCKH (SEQ ID NO: 9); HKHCH (SEQ ID NO: 10); HKHCKH (SEQ ID NO: 11); HKHC (SEQ ID NO: 12); HHHK(S)HHCKHHH (SEQ ID NO: 13); and HHK(S)HHKCHH(S)HHH (SEQ ID NO: 14), wherein the targeting ligand is linked to the side chain of the cysteine residue and the first oligonucleotide is linked to the side chain of a lysine residue, and wherein (S) is:
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The ‘714 Patent does not teach the therapeutic oligonucleotide inhibits expression of PCSK9 gene and comprises a sequence selected from the group consisting of SEQ ID NO:13. 15-21, 23-42 and 73-87 of the present invention.
Alnylam teach and suggests a siRNA molecule as now recited in the amended claims. For example, Alnylam teach a particular siRNA nucleic acid which comprises SEQ ID NO: 22 of the present invention. See Sequence 1336 of Alnylam. NOTE: Regarding SEQ ID NO: 25 of the present invention, Alnylam teach the dsRNA of their invention comprise different backbone chemistries including, alternating 2'-O-methyl and 2'-fluoro modified nucleotides, for example.
It would have been obvious and one of skill in the art would have been motivated to modify the teachings of the ‘714 Patent to include a PCSK9 siRNA comprising SEQ ID NO: 22 of the present invention since the ‘714 Patent taught a peptide docking vehicle for targeted nucleic acid delivery and Alnylam taught the desire to use gene therapy to target PCSK9 gene and protein expression using SEQ ID NO: 22 of the present invention since.
The present claims embrace, encompass and overlap in scope with claims 1-12 of the ‘714 Patent in view of Alnylam.
A terminal disclaimer disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of U.S. Patent No. 12054714 is required, or some other appropriate action.
THIS ACTION IS MADE FINAL. 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 Terra C. Gibbs whose telephone number is 571-272-0758. The Examiner can normally be reached from 8 am - 5 pm M-F.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Ram Shukla can be reached on 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TERRA C GIBBS/Primary Examiner, Art Unit 1635
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