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 . 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.
Election/Restrictions
Applicants elected the conjugate K(H3K)4C-Maleimide-PEG1000-folate without traverse in the reply filed on 5 May, 2025 and the phone call with Paul Booth, applicant’s representative on 27 May, 2025. In the response of 4 Dec, 2025, the claims were amended so that this species no longer reads on the claims. This is treated similarly to if the elected species was found allowable, i.e. the search is expanded to the independent claim and stopped when one or more references are found that read on that claim.
Claims Status
Claims 1, 8, 23, 24, 29, 30, 38-40, 43, 44, 47, 63, and 64 are pending.
Claims 63 and 64 are new.
Claims 8, 23, 24, 29, 30, 38-40, 43, 44, and 47 have been withdrawn from consideration due to an election/restriction requirement.
Maintained/Modified Objections
Drawings
The drawings are objected to because there are figures with sequences, but not SEQ ID numbers, note fig 2, for example. The MPEP states that "It should be noted that when a sequence is presented in a drawing, regardless of the format or the manner of presentation of that sequence in the drawing, the sequence must still be included in the sequence listing and the sequence identifier ("SEQ ID NO:X") must be used, either in the drawing or the brief description of the drawings” (MPEP 2422.02). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
response to applicant’s arguments
Applicants state that they have amended the specification to correct this issue.
Applicant's arguments filed 4 Dec, 2025 have been fully considered but they are not persuasive.
Applicants have corrected most of the drawings, but fig 2 has an image of a polypeptide sequence as a structure, without a corresponding SEQ ID number.
Sequence Listing
The sequence listing is objected to because there are no sequences in the sequence listing. The application file has a sequence listing that was submitted on 13 June, 2022, but that listing has no sequences in it.
Appropriate correction is required.
response to applicant’s arguments
Applicants state that the Patent Center shows a sequence listing filed on 13 June, 2022.
Applicant's arguments filed 4 Dec, 2025 have been fully considered but they are not persuasive.
The files with the application show a sequence listing with no sequences.
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. While applicants have clearly uploaded a sequence listing, there is some problem and it has not made it to the application file.
Withdrawn Rejections
Claims 1, 8, 14, and 16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph due to “cell specific targeting ligand” is hereby withdrawn due to amendment.
The rejection of claim 8 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite due to inconsistencies in the disclosure of peptide sequences is hereby withdrawn due to amendment. Note that HKC1 was given as an example, and the claim is now withdrawn. Should it be rejoined, the issue will resurface.
The rejection of claim 16 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite due to uncertainty as to number of targeting ligands in the context of multivalency is hereby withdrawn due to amendment.
The rejection of claim(s) 1, 14, and 16 under 35 U.S.C. 102(a)(1) as being anticipated by Berniger et al (US 20110312877) is hereby withdrawn due to amendment.
The rejection of claim(s) 1, 8, 14, and 16 under 35 U.S.C. 103 as being unpatentable over Berniger et al (US 20110312877) in view of Venables et al (US 20210180089, 102(a)(2) date 14 Aug, 2018), Yang et al (Sci. Rep. (2014) 4:7072), and Duan et al (CN 107793388) is hereby withdrawn due to amendment.
The provisional rejection of claims 1, 14, and 16 on the ground of nonstatutory double patenting as being unpatentable over claim 56 of copending Application No. 17/103,386 (US 20210162067) in view of Berniger et al (US 20110312877) is hereby withdrawn due to the abandonment of the competing application.
The rejection of claims 1, 14, and 16 on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5 of U.S. Patent No. 11,058,779 in view of Berniger et al (US 20110312877) is hereby withdrawn due to amendment.
The rejection of claims 1, 14, and 16 on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 7 of U.S. Patent No. RE46,873 in view of Berniger et al (US 20110312877) is hereby withdrawn due to amendment.
The rejection of claims 1, 14, and 16 on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 10 of U.S. Patent No.8,691,781 in view of Berniger et al (US 20110312877) is hereby withdrawn due to amendment.
Maintained/Modified Rejections
Claim Rejections - 35 USC § 103
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) 1, 63, and 64 are rejected under 35 U.S.C. 103 as being unpatentable over Berniger et al (US 20110312877) in view of Venables et al (US 20210180089, 102(a)(2) date 14 Aug, 2018). Please note that this rejection does not read on applicant’s elected species.
Berniger et al discusses targeted nanoparticles that can deliver various cargos(abstract). An example of a suitable cargo is siRNA (paragraph 171). Embodiments include a ligand attached to a polycationic species via a PEG linker, which can use a maleimide to connect (paragraph 19). The PEG can vary from only a few monomer units to very large (paragraph 168). An example is given where the sequence KHHHKHHHKHHHKHHHK (paragraph 245) is attached to the side chains of oligoornithine (paragraph 247). PEG is attached to a cyclic RGD sequence using NHS ester chemistry (paragraph 249), and a vinyl sulfone on the other side of the PEG chain is attached to the oligoornithine (paragraph 251). Note that the oligoornithine was synthesized with a Cys residue on the C-terminus specifically to selectively react with the vinyl sulfone (paragraph 204). While this example uses a branched sequence, linear sequences are contemplated (paragraph 147).
The difference between this reference and the examined claims is that this reference, while briefly mentioning unbranched sequences, does not mention a linear Lys/His sequence.
Venables et al discuss nanoparticles for delivery of nucleic acids to target cells, where the nucleic acid is bound to a cationic peptide bound to a hydrophilic polymer via a chelator (abstract). The cationic sequence comprises a majority of two amino acids selected from His and Lys and analogs (paragraph 17). Dendritic sequences comprising KHHHKHHHKHHHKHHHK are described, as well as similar linear sequences (table 1, p3). The important feature is the charge, with preferably at least 10 positively charged amino acids (paragraph 90). This reference describes similar linear sequences to those of Berniger et al, for the same purpose, and describes what is required for that purpose.
Therefore, it would be obvious to use a linear sequence instead of the branched sequence of Berniger et al, as Venables et al teaches linear sequences for the same purpose, and describes requirements for the sequence that are met by the linear sequences of Berniger et al. As Berniger et al explicitly mentions linear sequences, an artisan in this field would attempt this modification with a reasonable expectation of success.
These references render obvious the linear sequence KHHHKHHHKHHHKHHHKC-PEG-cRGD, as the oligoornithine of Berniger et al is used for branching, so would be unnecessary for a linear sequence. This has K(HHHK)4C, with the linker being a bond and the binding sequence cRGD, rendering obvious claim 1.
There is a PEG chain between the Cys residue of the peptide and the cRGD sequence, rendering obvious claims 63 and 64.
response to applicant’s arguments
Applicants argue that Berniger et al does not anticipate the claims, and Venables et al does not remedy the issue.
Applicant's arguments filed 4 Dec, 2025 have been fully considered but they are not persuasive.
Berniger et al, while not explicitly discussing K(HHK)4XC, explicitly discusses linear sequences, for which the oliogornithine would not be required. It at least suggests this sequence, and Venables et al states what is required of similar sequences, leading to a reasonable expectation of success and more direction to linear sequences.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
first rejection
Claims 1, 63, and 64 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 13 of copending Application No. 18/909,519 in view of Berniger et al (US 20110312877).
Competing claim 13 describes a method of treatment, comprising administering an siRNA slong with HKP(+H). This is defined as a histidine/lysine peptide comprising KHHHKHHHKHHHKHHHK (paragraph 94).
The difference between the competing claims and the examined claims is that the competing claims do not discuss a targeting moiety attached via a Cys.
Berniger et al discusses targeted nanoparticles that can deliver gene expression cassettes (abstract). Embodiments include a ligand attached to a polycationic species via a PEG linker, which can use a maleimide to connect (paragraph 19). The PEG can vary from only a few monomer units to very large (paragraph 168). An example is given where the sequence KHHHKHHHKHHHKHHHK is attached to (paragraph 245) is attached to the side chains of oligoornithine (paragraph 247). PEG is attached to a cyclic RGD sequence using NHS ester chemistry (paragraph 249), and a vinyl sulfone on the other side of the PEG chain is attached to the oligoornithine (paragraph 251). Note that the oligoornithine was synthesized with a Cys residue on the C-terminus specifically to selectively react with the vinyl sulfone (paragraph 204).
Therefore, it would be obvious to use the targeting moiety of Berniger et al to deliver the si RNA of the competing claims. As the competing claims use the same peptide as this construct, an artisan in this field would attempt this modification with a reasonable expectation of success.
response to applicant’s arguments
Applicants argue that the rejection does not make a prima facie case that claim 1 is obvious.
Applicant's arguments filed 4 Dec, 2025 have been fully considered but they are not persuasive.
Applicants have not explained why the case made that the competing claims render the examined claims obvious is invalid or incorrect. The argument presented, that the case was not made, without an explanation of why the case was not made, is merely a statement of disagreement with the rejection.
second rejection
Claims 1, 63, and 64 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 8 of U.S. Patent No. 11,697,813 in view of Berniger et al (US 20110312877).
Competing claim 1 describes a method of treatment, comprising administering an siRNA salong with a histidine/lysine polymer. Competing claim 8 specifies that the histidine/lysine copolymer comprise the sequence KHHHKHHHKHHHKHHH.
The difference between the competing claims and the examined claims is that the competing claims do not discuss a targeting moiety attached via a Cys.
Berniger et al discusses targeted nanoparticles that can deliver gene expression cassettes (abstract). Embodiments include a ligand attached to a polycationic species via a PEG linker, which can use a maleimide to connect (paragraph 19). The PEG can vary from only a few monomer units to very large (paragraph 168). An example is given where the sequence KHHHKHHHKHHHKHHHK is attached to (paragraph 245) is attached to the side chains of oligoornithine (paragraph 247). PEG is attached to an RGD sequence using NHS ester chemistry (paragraph 249), and a vinyl sulfone on the other side of the PEG chain is attached to the oligoornithine (paragraph 251). Note that the oligoornithine was synthesized with a Cys residue on the C-terminus specifically to selectively react with the vinyl sulfone (paragraph 204).
Therefore, it would be obvious to use the targeting moiety of Berniger et al to deliver the si RNA of the competing claims. As the competing claims use the same peptide as this construct, an artisan in this field would attempt this modification with a reasonable expectation of success.
response to applicant’s arguments
Applicants have used the same arguments for all double patenting rejections.
Conclusion
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 FRED REYNOLDS whose telephone number is (571)270-7214. The examiner can normally be reached M-Th 9-3:30.
Examiner interviews are available via telephone 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, Melissa Fisher can be reached at 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/FRED H REYNOLDS/Primary Examiner, Art Unit 1658