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 .
Restriction/Election
Applicant’s election without traverse of the CPP cyclo[FFFRRQ] (SEQ ID NO: 39), linked by divalent 8-amino-3,6-dioxaoctanoic acid to the “P” tetrapeptide KKKK, and the cargo siLuc antisense oligonucleotide, SEQ ID NO: 140, in the reply filed on 06/29/26 is acknowledged.
There are no claims that comprise these species together and no embodiments in the specification that reduce this combination to practice, so the search was conducted for each species in the context of the present claims, which read on claims 1-4, 7, 11, 13, 16-19, 24 and 28. The elected species were found, but additional species were revealed throughout the search, which read on claims 5, 6, 8-10, 12, 14 and 15 as well. As such, these claims were also examined.
Claims 20-23, 26 and 27 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species or non-prior art species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/29/26.
Claims 1-19, 24, 25 and 28 are under examination. An Office action on the merits follows.
Claim Rejections 35 USC 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-19, 24, 25 and 28 are 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). The term “CPP” in claim 1 is used by the claim to mean “cyclic peptide conjugate,” while the accepted meaning is “cell-penetrating peptide.”
The term is indefinite because the specification does not clearly redefine the term, as it states [at 0161] “As used herein, ‘cell penetrating peptide’ or ‘CPP’ refers to any peptide which is capable of penetrating a cell membrane. As used herein, ‘cyclic cell penetrating peptide’ or ‘cCPP’ refers to any cyclic peptide which is capable of penetrating a cell membrane.” There is nowhere in the specification that the term “cyclic polypeptide conjugate” is explicitly stated or called a CPP or a cyclic CPP. Furthermore, “polypeptide conjugate,” is unclear, as a conjugate generally would refer to the conjugate itself, and not refer to a peptide portion of the conjugate as the conjugate itself. Appropriate clarification is required.
For purposes of examination, the term “CPP” will be considered a cyclic peptide having the inherent function of a “cell penetrating peptide” because this is what it is termed in the art, as well as in the specification.
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.
Claim(s) 1, 4-12, 14, 15, 17-19, 24, 25 and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Pei et al. (US2017/0355730).
Broadest Reasonable Claim Interpretation
Claim 1 is drawn to a CPP, which will be considered any cyclic peptide, as the terminology is unclear and inconsistent with the accepted meaning. The linker can comprise any additional functional groups, provided it has at least one ethylene glycol is present in the linker structure, and P can be any peptide with at least three of the recited amino acid residues. As to the cargo and the configuration of the components of the formula in claim 1, there is no attachment point, and no guidance in the specification that limits the formula to a particular configuration with the cargo. As such, cargo can be covalently or non-covalently attached and can be any chemical moiety that interacts with the CPP-linker-P combination at any location on the CPP, linker or P.
Pei teaches compounds can comprise a cell penetrating peptide moiety and a cargo
moiety, wherein the cargo moiety can comprise one or more detectable moieties, one or more
therapeutic moieties, one or more targeting moieties, or any combination thereof [abstract]. In
the embodiments, the cell penetrating peptide moiety is cyclic or the cell penetrating peptide
moiety is cyclic and the cargo moiety is appended to the cyclic cell penetrating peptide moiety
structure [abstract]. This reference teaches that the plasma membrane presents a major challenge
in drug discovery, especially for biologics such as peptides, proteins and nucleic acids, and potential strategy to subvert the membrane barrier and deliver the biologics into cells is to attach them to cell-penetrating peptides (CPPs) for translocation into the cells, where the cargo moiety is a nucleic acid that is targeted for delivery to the target cell. [0003, 0202]. Pei teaches many species of peptides that fall within the broad genus of CPPs in claim 1:
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Pei specifically demonstrated that demonstrated that cFΦRRRR is effective for exocyclic
delivery of small-molecules, peptides, and protein cargos into the cytoplasm and nucleus of
mammalian cells, and that using a pCAP-containing peptide as cargo/reporter, it was shown that
cFΦRRRR can be 3.7-12-fold more efficient than R9, Tat, and Antp for cytoplasmic cargo
delivery, making cFΦRRRR one of the most active CPPs known to date [0269]. Pei
teaches various embodiments of c(FΦRRRRQ)-K(FITC) (FIG. 35A) and c(fΦRrRrQ)-K(FITC)
(FIG. 35B), where Q is used to link the CPP with the cargo peptide or polyamine through both
PEG, disulfide bonds and/or amino acid linkers [0062].
With regard to the cargo moiety in the CPP-linker-cargo motif, Pei teaches that the cargo may be a linker moiety, a detectable moiety, a therapeutic moiety, a targeting moiety (specifically a targeting nucleic acid), and the like, with the linker 8-amino-3,6-dioxaoctanoic acid (i.e., miniPEG) [0119].
Specifically, Pei teaches examples of the cargo moiety listed in Table 4, or derivatives or
combinations thereof:
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Several of these peptides anticipate the compounds of instant claims, and SEQ ID NO 90:
cyclo(FΦRRRRQ)-RRRRR-K(Rho) anticipates instant claim 1 by teaching a) a group that binds
to a nucleic acid sequence by electrostatic interactions (P) comprising at least three monomers of
arginine, and b) at least one CPP comprising at least two arginines. Specifically, the conjugates of Pei fall within the genus of structure (c) CPP-L- ([P]m)s, where CPP and P are as described, m is 1 and S is 1.
Pei also teaches that compound with a linker having miniPEG in combination with the CPP and cargo with a linker comprising –(CH2-CH2-O-)z:
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(FIG. 17F).
Pei teaches these compounds having L as the linker, 8-amino-3,6-dioxaoctanoic acid (abstract reciting minPEG) covalently attaching CPPs to P and/or cargo. As such, the linker here a can comprises –(CH2-CH2-O-)z, attached to the CPP c[FΦRRRR] and peptide P or cargo (as cargo has no structural requirement or attachment point).
The difference between the prior art and the instant claims is that the prior art does not teach P as a polypeptide comprising at least three of Arg, Lys, and His attached to the linker.
However, as discussed above, there is no description in the claims as to how the compound also comprises a cargo moiety. As such, the “cargo” of Pei, listed in table 4, can also be considered a moiety attached to the CPP, which is only requires to have three of R, K or H. Because Pei teaches the tetrapeptide RRRR as an attached cargo moiety itself, the structure of claim 1 can also be construed as an RRR monomer that is P, where m and s are each 1, and any of the additional peptides (i.e., the 4th-5th arginines of the RRRRR), or the peptides shown in structure 2-PCP can serve separately as cargo, as there is nothing in claim 1 that limits the first three monomers (RRR) from serving as the structure of P, and the fourth and fifth RR as the structure of the cargo (as it is any chemical moiety, including an amino acid).
As such, it would have been obvious to one of ordinary skill in the art at the filing date of the invention to have taken the CPP-linker-cargo taught in different embodiments of Pei and combined the CPP with the mini-PEG linker and RRRRR P/cargo because Pei teaches that these are all effective for delivery into cells together. One would be motivated to do so because Pei teaches that these CPP-linker conjugates enhance the ability of cargo transfection into cells through the membrane. As such, there is a reasonable expectation of success that RRRRR can be delivered by the CPP-linker (1-PCP) system effectively.
This meets the limitations of claim 1 by teaching each and every limitation claimed: P is any peptide with any three lysine, arginine, histidine residue or any combination of three at any location in the peptide, and CPP is any cyclic peptide, meaning that cFΦRRRR meets this limitation. M and s are 1, which does not limit the peptide, but rather allows it to be any repeating or non-repeating peptide sequence. The linker “L,” is only limited in that somewhere in the structure, there must but an ethylene glycol, which is met be the prior art teaching of the elected species linker 8-amino-3,6-dioxaoctanoic acid (i.e., miniPEG) between the CPP and P/cargo. As to the cargo, there is nothing in claim 1 that requires any particular cargo, meaning any chemical portion of this structure can be considered cargo, if it is transported by the CPP, linker and an additional peptide that includes three of the claimed monomers, or it can be considered the P peptide and the cargo together or recited generically (as it is in the claim), and as is taught in Pei. There is nothing in the claims designating how the cargo is attached to the claimed compound, and nothing limiting the additional components and moieties that can be attached to the formula, as the cargo can be attached at any point, either covalently or non-covalently, and it has no structure or function required.
Claim 4 is met because the P elected is 4 monomers, and the P taught by Pei teaches 4 Arginine monomers. Claims 5 and 8-10 are met by the CPP’s of Table 2 above, which teach 4-9 monomers. Claims 6, 11 and 12 are met because the CPP’s of Pei include arginine, and some embodiments are all natural amino acids (e.g., SEQ ID NOs: 15, 19, 20, 27, 29). Claim 7 is met because Pei teaches that these are cell penetrating peptides. Claims 14, 24 and 25 are met because Pei teaches CPP’s, such as SEQ ID NO 27: FWRRR. Claim 15 is met because Pei teaches that the cargo may be a therapeutic agent. Claim 17 is met because the CPP’s of Pei are D or L and they are 5-9 residues. Claims 18 and 19 are met for the same reasons as claim 14, as they require the same arginine and hydrophobic side chains for the CPP. Claim 28 is met because the same linker, 8-amino-3,6-dioxaoctanoic acid, is taught.
Claim(s) 1-19, 24, 25 and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Pei et al. (US2017/0355730), as applied to claims 1, 4-12, 14, 15, 17-19, 24, 25 and 28 above, in view of Rozners et al. (US10,260,089).
The teachings of Pei have been described supra.
The difference between the prior art and the instant claims is that the prior art does not teach the elected species for P, (Lys)4, or antisense oligonucleotides as cargo.
Rozners teaches that conjugation of short peptide nucleic acids (PNAs) with tetralysine peptides strongly enhanced triple helical binding to RNA at physiologically relevant conditions (Col. 11, lines 60-67). This reference teaches that PNA hexamers and heptamers carrying cationic nucleobase and tetralysine modifications displayed high binding affinity for complementary double-stranded RNA without compromising sequence selectivity, and that the conjugates had unique preference for binding double-stranded RNA, while having little affinity for double-stranded DNA, and they were efficiently taken up by HEK293 cells, whereas little uptake was observed for unmodified PNA (Col. 12, lines 1-25, FIG. 5). This reference further teaches that PNA bearing cationic α- and γ-substituents bind strongly to cDNA and RNA and exhibit interesting biological properties with antisense effects (Spanning Col. 27-28)
It would have been obvious to one of ordinary skill in the art at the filing date of the invention to have taken the (Lys)4 of Rozners and conjugated it to a CPP-linker in order to deliver antisense oligonucleotides because Rozners teaches that this cationic modification increases its binding affinity for RNA and that only the cationic modified PNAs were efficiently taken up by cells compared to unmodified PNAs. One would be motivated to do so because attaching the (Lys)4 to the peptide-linker of Pei delivering antisense oligonucleotides with cationic peptides increases the nucleic acid binding affinity for RNA, which is the target of antisense, and it aids the CPP of PNA’s in cellular uptake of the nucleic acid cargo. As such, there is a reasonable expectation of success that the (Lys)4 of Rozners will effectively aid in the cellular uptake of antisense oligonucleotides that target their intended RNA when combined with the CPP-linker of Pei.
This meets the limitations of claims 2, 3, 13 and 16 by rendering it obvious to have used (Lys)4 as P and an antisense oligonucleotides as the cargo.
Claim(s) 1-19, 24, 25 and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Pei et al. (US2017/0355730), as applied to claims in view of Rozners et al. (US10,260,089), and in further view of Qian and Pei (WO2018/098231).
Qian teaches cyclic cell-penetrating peptides that delivery biologically active moieties into cells (abstract). This reference teaches that CPP’s such as SEQ ID NO 10: c(FΦRRRRQ), and similar CPPs, such as SEQ ID NO 66: FFFRRQ, are used to attach and transport nucleic acids that are targeted for delivery to the target cell [0016, 0198]. This reference also teaches that linkers, such as 8-amino-3,6-dioxaoctanoic acid (miniPEG) can be used in the conjugate [0134].
It would have been obvious to one of ordinary skill in the art at the filing date of the invention to have taken the CPP of Qian and used it as the CPP of Pei because they are both know to be CPPs that delivery nucleic acid cargo into cells. One would be motivated to use the CPP of Qian in the conjugate of Pei because Qian teaches the same type of CPP for the same function with the same linker for delivering cargo. As such, there is a reasonable expectation of success that the cargo of Pei can be effectively delivered with the CPP (SEQ ID NO: 66) of Qian.
Although it is not claimed, this renders obvious the elected species of CPP, SEQ ID NO: 39.
Claim(s) 1-19, 24, 25 and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Pei et al. (US2017/0355730) in view of Rozners et al. (US10,260,089), and in further view of Ishihara et al. (Drug Delivery, 2009; 16(3): 153–159) as evidenced by Lee et al. (WO2012/125987).
Note that although the same claims are all rejected, this is solely to address the elected species, which not claimed.
The difference between the prior art and the elected species is that the prior art does not teach that the cargo is siLuc antisense.
Ishihara teaches intracellular delivery of siRNA by cell-penetrating peptides modified with cationic oligopeptides, or “CPP-CP” complexes (abstract). This reference teaches that anti-Luciferase SiRNAs are designed to target GL3 luciferase mRNA (Control siRNA duplex Firefly Luciferase GL3) and designed to minimize sequence homology with any known vertebrate transcript to be used as a control for CPP siRNA delivery (p. 154, Col. 2). Ishihara teaches specifically that the silencing activity of siRNA complexes formed with CPP-CP conjugates was determined by using the exogenous luciferase gene, anti-Luc as the negative control (Figure 6). The experimental data using Si-Luc complexes formed with TP-K6 and TP-H 6K6 showed high specific silencing activity, while those with CPP alone and Pen-K 10 showed almost no activity (p. 157, Col. 2, para. 2).
It would have been obvious to one of ordinary skill in the art at the filing date of the invention to have taken the si-Luc of Ishihara and conjugated it to the CPP-linker-peptides of Pei and Rozners as a control siRNA. One would be motivated to do so because Ishihara teaches that it is used as a control to minimize sequence homology with any known vertebrate transcript and test CPP-CP delivery into cells in a similar system to that of Pei and Rozners, using Lysine cationic peptides and CPPs. As such, there is a reasonable expectation of success that the siLuc of Ishihara can be delivered by the complex of Pei and/or Rozners.
Although this cargo is not claimed, this combination renders obvious both the elected species of siLuc, SEQ ID NO: 140, as evidenced by Lee (SEQ ID NO: 20) and (Lys)4 in a CPP-L-P complex with antisense cargo.
Non-Statutory 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.
Claims 1, 4-12, 14, 15, 17-19, 24, 25 and 28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. 12,171,838. Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 teaches:
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As discussed above in the broadest reasonable interpretation, the claimed formula does not discuss where the cargo is attached or how, nor does it discuss the type of cargo. As such, additional -L-CPPs attached to the P are within the scope of the cargo.
This meets the limitations of instant claims 1, 4-12, 14, 15, 17-19, 24, 25 and 28 by teaching the same CPP-L-P of claim 1 with the CPP having arginine and hydrophilic side chains and linker.
Claims 1-19, 24, 25 and 28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 12,171,838 in view of in view of Rozners et al. (US10,260,089).
The teaching of ‘838 have been described supra.
The difference between instant claims 2, 3, 13 and 16 and the claims of ‘838 is that the claims of ‘838 do not teach at least three lysine monomers or anti-sense oligonucleotides as the cargo.
The teachings of Rozners have been described supra.
It would have been obvious to one of ordinary skill in the art at the filing date of the invention to have taken the (Lys)4 of Rozners and conjugates it to the CPP-linker of ‘838 in order to deliver antisense oligonucleotides because Rozners teaches that this cationic modification increases binding affinity for RNA and only the cationic peptide modified PNAs were efficiently taken up by cells compared to unmodified PNAs. One would be motivated to do so because attaching the (Lys)4 to the peptide-linker of ‘838 because delivering antisense oligonucleotides with such cationic peptides increases the nucleic acid binding affinity for RNA, which is the target of antisense, and aids the CPP in cellular uptake of the nucleic acid cargo. As such, there is a reasonable expectation of success that the (Lys)4 of Rozners will effectively aid in the cellular delivery of antisense oligonucleotides that target the intended RNA when combined with the CPP-linker of ‘838.
Claims 1, 4-12, 14, 15, 17-19, 24, 25 and 28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 101-120 of copending Application No. 18/950,272. Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 teaches:
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The structure may be:
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This meets the limitations of instant claims 1, 4-12, 14, 15, 17-19, 24, 25 and 28 by teaching the same CPP-L-P of claim 1 with the CPP having arginine and hydrophilic side chains and linker.
This is a provisional nonstatutory double patenting rejection.
Claims 1-19, 24, 25 and 28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 101-120 of copending Application No. 18/950,272 in view of in view of Rozners et al. (US10,260,089). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘272 do not teach at least three lysine monomers or anti-sense oligonucleotides as the cargo.
The teachings of Rozners have been described supra.
It would have been obvious to one of ordinary skill in the art at the filing date of the invention to have taken the (Lys)4 of Rozners and conjugates it to the CPP-linker of ‘272 in order to deliver antisense oligonucleotides because Rozners teaches that this cationic modification increases binding affinity for RNA and only the cationic peptide modified PNAs were efficiently taken up by cells compared to unmodified PNAs. One would be motivated to do so because attaching the (Lys)4 to the peptide-linker of ‘272 because delivering antisense oligonucleotides with such cationic peptides increases the nucleic acid binding affinity for RNA, which is the target of antisense, and aids the CPP in cellular uptake of the nucleic acid cargo, as well as acting as a CPP itself. As such, there is a reasonable expectation of success that the (Lys)4 of Rozners will effectively aid in the cellular delivery of antisense oligonucleotides that target the intended RNA when combined with the CPP-linker of ‘272.
This is a provisional nonstatutory double patenting rejection.
Claims 1-19, 24, 25 and 28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 146-174 of copending Application No. 18/390,717. Although the claims at issue are not identical, they are not patentably distinct from each other because claim 146 teaches:
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Claim 170 teaches the structure:
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, which contains the same CPP-L-P (where P is EC), and the linker has the ethylene glycol, and the cargo is attached in some way to the complex. The instant claims do not exclude additional moieties or designate points of attachment outside of the linker being attached to two different peptides, one of which must be cyclic, and the other a must contain three of K, R and/or H.
This meets the limitations of instant claims 1-19, 24, 25 and 28 by teaching the same CPP-L-P of claim 1 with the CPP having arginine and hydrophilic side chains and linker, lysine monomers and antisense oligomers.
This is a provisional nonstatutory double patenting rejection.
Claims 1-2, 4-15, 17-19, 24, 25 and 28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 46-71 of copending Application No. 18/858,718. Although the claims are not identical, they are not patentably distinct because claim 46 teaches:
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Claim 61 teaches KKKK as the P monomer.
This meets the limitations of instant claims 1, 4-12, 14, 15, 17-19, 24, 25 and 28 by teaching the same CPP-L-P of claim 1 with the CPP having arginine and hydrophilic side chains and linker.
This is a provisional nonstatutory double patenting rejection.
Claims 1-19, 24, 25 and 28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 146-174 of copending Application No. 18/858,718 in view of in view of Rozners et al. (US10,260,089).
The difference between instant claims 2, 3, 13 and 16 and the claims of ‘718 is that the claims of ‘717 do not teach anti-sense oligonucleotides as the cargo.
The teachings of Rozners have been described supra.
It would have been obvious to one of ordinary skill in the art before the filing date of the invention to have taken the (Lys)4 of Rozners and conjugates it to the CPP-linker of ‘718 in order to deliver antisense oligonucleotides because Rozners teaches that this cationic modification increases binding affinity for RNA and only the cationic peptide modified PNAs were efficiently taken up by cells compared to unmodified PNAs. One would be motivated to do so because attaching the (Lys)4 to the peptide-linker of ‘718 because delivering antisense oligonucleotides with such cationic peptides increases the nucleic acid binding affinity for RNA, which is the target of antisense, and aids the CPP in cellular uptake of the nucleic acid cargo, as well as acting as a CPP itself. As such, there is a reasonable expectation of success that the (Lys)4 of Rozners will effectively aid in the cellular delivery of antisense oligonucleotides that target the intended RNA when combined with the CPP-linker of ‘718.
This is a provisional nonstatutory double patenting rejection.
Claims 1-2, 4-15, 17-19, 24, 25 and 28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 111-133 and 135 of copending Application No. 18/553,379. Although the claims are not identical, they are not patentably distinct because claim 111 teaches formula IIb, which comprises the same CPP-L-P with the same lysine or arginine residues, claim 112 teaches the same linker and claim 121 teaches KKKK as the P monomer.
This is a provisional nonstatutory double patenting rejection.
Claims 1-19, 24, 25 and 28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 111-133 and 135 of copending Application No. 18/553,379 in view of in view of Rozners et al. (US10,260,089).
The difference between instant claims 2, 3, 13 and 16 and the claims of ‘718 is that the claims of ‘717 do not teach anti-sense oligonucleotides as the cargo.
The teachings of Rozners have been described supra.
It would have been obvious to one of ordinary skill in the art before the filing date of the invention to have taken the (Lys)4 of Rozners and conjugates it to the CPP-linker of ‘379 in order to deliver antisense oligonucleotides because Rozners teaches that this cationic modification increases binding affinity for RNA and only the cationic peptide modified PNAs were efficiently taken up by cells compared to unmodified PNAs. One would be motivated to do so because attaching the (Lys)4 to the peptide-linker of ‘379 because delivering antisense oligonucleotides with such cationic peptides increases the nucleic acid binding affinity for RNA, which is the target of antisense, and aids the CPP in cellular uptake of the nucleic acid cargo, as well as acting as a CPP itself. As such, there is a reasonable expectation of success that the (Lys)4 of Rozners will effectively aid in the cellular delivery of antisense oligonucleotides that target the intended RNA when combined with the CPP-linker of ‘379.
This is a provisional nonstatutory double patenting rejection.
Claims 1-19, 24, 25 and 28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 79-105 of copending Application No. 18/688,083. Although the claims are not identical, they are not patentably distinct because claim 79 teaches formula IIb, which comprises the same CPP-L-P with the same lysine or arginine residues, the same linker and claim 84 teaches at least three lysines as the P monomers (EP) and claim 96 teaches antisense oligonucleotide cargo.
This is a provisional nonstatutory double patenting rejection.
Claims 1-19, 24, 25 and 28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 130-172 of copending Application No. 18/289,946. Although the claims are not identical, they are not patentably distinct because claim 130 teaches the same CPP-L-P, with the same lysine or arginine residues in the EP, and the same linker and claim 132 teaches at least three lysines as the P monomers (EP) and antisense oligonucleotide cargo (claim 130).
This is a provisional nonstatutory double patenting rejection.
Claims 1-19, 24, 25 and 28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 74-99 of copending Application No. 18/688,096. Although the claims are not identical, they are not patentably distinct because claim 74 teaches a compound which comprises the same CPP-L-P with the same lysine or arginine residues, the same linker, at least three lysines as the P monomers (EP) and AC as the antisense oligonucleotide cargo.
This is a provisional nonstatutory double patenting rejection.
Claims 1-19, 24, 25 and 28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 141-162 of copending Application No. 18/289,944. Although the claims are not identical, they are not patentably distinct because claim 141 teaches a compound, which comprises the same cCPP-L-P with the same lysine or arginine and hydrophobic residues, the same linker, at least three lysines as the P monomers (EP) and an antisense oligonucleotide cargo.
This is a provisional nonstatutory double patenting rejection.
Claims 1-19, 24, 25 and 28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 79-105 of copending Application No. 18/506,057. Although the claims are not identical, they are not patentably distinct because claim 1 teaches a compound comprising the same CPP-L-P with the same lysine or arginine residues, the same linker and claim 84 teaches at least three lysines as the P monomers (EP) and claim 96 teaches antisense oligonucleotide cargo.
This is a provisional nonstatutory double patenting rejection.
Conclusion
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/JEANETTE M LIEB/Primary Examiner, Art Unit 1654
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