CELL-PENETRATING PEPTIDE COMPOUNDS

§112 §DP

DETAILED ACTION Examiner acknowledges receipt of the replies filed 12/19/2025 and 3/9/2026, in response to the restriction requirement mailed 10/28/2025. Claims 1-12 are pending. Claims 2-4 and 8-11 are withdrawn from further prosecution for the reasons set forth below. Claims 1, 5-7, and 12 are being examined on the merits in this office 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 The filing receipt dated 10/02/2025 provides the following information: PNG media_image1.png 138 452 media_image1.png Greyscale Election/Restrictions Applicant’s election of the following species without traverse in the reply filed on 3/09/2026 is acknowledged. Cyclic peptide: SEQ ID NO:110, PNG media_image2.png 67 125 media_image2.png Greyscale targeting moiety: PNG media_image3.png 37 343 media_image3.png Greyscale linker: 8-amino-3,6,dioxaoctanoic acid therapeutic moiety: dexamethasone PNG media_image4.png 55 641 media_image4.png Greyscale PNG media_image5.png 198 615 media_image5.png Greyscale Reply filed 3/9/2026 at pp. 4-5. Claims 1, 5-7, and 12 read on the elected species. Claims 2-4 and 8-11 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 3/9/2026. Status identifiers of withdrawn claims should be revised in reply to this office action. Upon searching the elected species, an additional species was found. Accordingly, for purposes of compact prosecution, the election of species is modified only to the extent of examining this additional species. Otherwise the election of species requirement is still retained. Specification Please note, the specification has not been checked to the extent necessary to determine the presence of all possible error. Applicant's cooperation is required in correcting any errors of which applicant may become aware in the specification. MPEP § 608.01. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. See as-filed specification at para [0093]. Claim Rejections - 35 USC § 112 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, 5-7, and 12 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. Claim 1, and claims dependent on it, requires at least 2 hydrophobic amino acids. However, while the concept of hydrophobicity and hydrophilicity are well understood, there is no art recognized cutoff between hydrophobic and not hydrophobic. For example, serine and threonine are considered hydrophobic in claim 7 of US 5,670,483, but the Thermo Fisher web page for amino acid properties (downloaded March, 2026) lists these amino acids as hydrophilic. This shows up in applicant's disclosure, where a number of different cutoffs are proposed (Table 2, para [0080]). This means that there is a genus of amino acids where it is unclear if they are hydrophobic or hydrophilic. Claim 1, and claims dependent on it, require a therapeutic moiety attached to the peptide. However, applicants have not defined what a therapeutic moiety is. Anything in a large enough dose will have a physiological effect (the dose makes the poison), but the physiological effect may not be desirable to all patients. Water is an active ingredient in some formulations (Reliance Medical Eye wash, package insert, (2018)), but also causes hyponatremia, which can be lethal. This makes it unclear what the term "therapeutic moiety" encompasses. The metes and bounds of claim 1, the claims dependent on it, are deemed to be indefinite. Claim 1 recites the term “targeting moiety”. This term is not defined in the specification. The term “targeting moiety” is a relative term which renders the claim indefinite. The term “targeting moiety” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Claims 5 and 12 recite the limitation "the natural stereoconfiguration". There is insufficient antecedent basis for this limitation in the claim. To overcome this rejection, examiner recommends that the respective claims be amended to recite "a [[the]] natural stereoconfiguration". The following is a quotation of the first paragraph of 35 U.S.C. 112(a): (a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention. The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112: The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention. Claims 1, 5-7, and 12 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated: “To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient.” MPEP 2163. Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co., the court stated: “A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials. Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284-85 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus. . . ."). Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398. The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP 2163. The MPEP does state that for generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP 2163. Although the MPEP does not define what constitute a sufficient number of representative, the Courts have indicated what do not constitute a representative number species to adequately describe a broad generic. In Gosteli, the Court determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gosteli, 872 F.2d at 1012, 10 USPQ2d at 1618. For written description, the analysis considers (a) Actual reduction to practice, (b) Disclosure of drawing or structural chemical formulas, (c) Sufficient relevant identifying characteristic in the way of complete/partial structure or physical and/or chemical properties, functional characteristics when coupled with known or disclosed and (d) Representative number of examples. In the instant case, the claims are drawn to cyclic peptides of formula I-C comprising 8 amino acids wherein one of the side chain of one of the 8 amino acids is coupled to a cargo moiety; wherein 2 or 3 of the amino acids are arginine, and the remaining amino acids are other than arginine; at least 2 of the amino acids are independently a hydrophobic amino acid; and wherein the cargo moiety comprises a linker moiety, a therapeutic moiety, and a targeting moiety. The claims encompass the numerous cyclic peptides comprising 2 arginine residues, at least two hydrophobic amino acid residues, without restriction as to identity, position, or spacing; permit all remaining amino acid positions to be occupied by any amino acid; include a cargo moiety conjugated to the side chain any amino acid within the cyclic peptide; and allow substantial variability in peptide length, residue order, residue composition, and cargo attachment location. However, the specification is very limited as to teaching specific compounds that fall within each of these claim terms. The claim terms “linker moiety”, “targeting moiety” and “therapeutic moiety” are not expressly defined in the specification. Table 5 discloses cargo moieties. Table 6 discloses example targeting moieties. The linker moiety, therapeutic moiety, and targeting moiety are not restricted to any particular chemical structure or physical composition. The linker moiety, therapeutic moiety, and targeting moiety, respectively, can each include, but are not limited to, saccharides, polymers, small molecules, proteins, lipids, nucleotides, and any combination thereof. (a) Actual reduction to practice/ (b) disclosure of drawing or structural chemical formulas: The specification discloses synthesis and testing of a limited number of cyclic cell-penetrating peptides (e.g., Table 4). The specification indicates that the claimed peptides are cell penetrating peptides that allow for cytosolic cargo delivery. However, of all the cell penetrating cyclic peptides disclosed in Table 4 only PNG media_image2.png 67 125 media_image2.png Greyscale (SEQ ID NO:110) satisfies all of the claimed requirements of instant claim 1 (2-3 arginine, at least 2 hydrophobic amino acids, and 8 amino acids in total length- of formula I-C). Thus, a single CPP of formula I-C is disclosed in the specification. No examples of a cyclic peptide conjugated to a cargo moiety were reduced to practice. (c) Sufficient relevant identifying characteristic in the way of complete/partial structure or physical and/or chemical properties, functional characteristics when coupled with known or disclosed: and (d) Representative number of examples: The invention involves an unlimited number of peptides of formula I-C, linker moieties, therapeutic moieties, and targeting moieties, and combinations thereof. Thus, the specification only provides guidance for a single peptide of formula I-C, SEQ ID NO:110. This is further complicated by the lack of guidance regarding the binding/coupling site of the cargo moiety to the cyclic peptide. The instant claims allow for the cargo moiety to be coupled to any one of the eight amino acid side chains within in the cyclic backbone of the peptide of formula I-C. However, there the specification lacks guidance as to side chains that would not be conducive for coupling the cargo moiety, e.g., attachment at an arginine side chain could disrupt the overall charge of the peptide. Examiner expressly notes that claim 1 was amended to remove a limitation reciting that the cargo moiety was coupled to a side chain of a glutamine in the cyclic peptide. As stated earlier, the MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic. It must not be forgotten that the MPEP states that if a biomolecule is described only by a functional characteristic (e.g., reduces a side effect associated with the other anticancer agent) and/or a functional/structural characteristic without any disclosed correlation between function and structure of the biomolecule beyond the examples presented, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed biomolecule.” MPEP 2163. Here, though the claims may recite some functional characteristics, and even some generic structural features and several distinct species are given (e.g. CPPs set forth in Table 1), the claims lack written description because there is no disclosure of a correlation between function and structure of the peptides of formula I-C, linker moieties, therapeutic moieties, and targeting moieties beyond those disclosed in the examples in the specification. It is further noted that certain components may not be chemically/physically compatible due to differences in pH, hydrophobic/hydrophilic, or solubility requirements. Accordingly, there are not only many distinct components (peptides of formula I-C, linker moieties, therapeutic moieties, and targeting moieties), there are also numerous combinations of components that fall within the instant claim scope to give rise to a claimed cyclic peptide. The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate"). The skilled artisan cannot extrapolate to the myriad cyclic peptides comprising numerous combinations of peptides of formula I-C, linker moieties, therapeutic moieties, and targeting moieties that fall within the instant claim scope based on a single peptide (SEQ ID NO:110) that was reduced to practice. Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention. 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. Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 11352394 (hereinafter referred to as the ‘394 patent). Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons. Regarding claim 1, claims 1-8, 11-14, 21, and 25 of the ‘394 patent teach a compound comprising a cyclic peptide having 8 amino acids comprising a cell penetrating peptide moiety, represented by the following structure: PNG media_image6.png 103 130 media_image6.png Greyscale , wherein AA1-AA8 are amino acids, wherein at least 2 amino acids are Arg, at least 2 amino acids comprise a hydrophobic side chain. Claims further teach that the compound further comprises cargo moiety. Claim 21 of the ‘394 patent teaches cargo, but silent on linker, therapeutic and detectable moieties on the cargo. However, specification defined cargo, which comprises linker, therapeutic and detectable moieties [see col.7, lines 9-42; col.28, lines 45-67]. Claim 1, 7 and 12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 12454552 (hereinafter referred to as the ‘552 patent). Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons. Regarding claim 1, claims 1-3 of the ‘552 patent teach a compound comprising a cyclic peptide having 8 amino acids comprising a cell penetrating peptide moiety, represented by the following structure: PNG media_image6.png 103 130 media_image6.png Greyscale , wherein AA1-AA8 are amino acids, wherein at least 3 amino acids are Arg, at least 2 amino acids comprise a hydrophobic side chain. Claims further teach that the compound further comprises cargo moiety. Claim 3 of the ‘552 patent teaches cargo, but silent on linker, therapeutic and detectable moieties on the cargo. However, specification defined cargo, which comprises linker, therapeutic and detectable moieties [see col.7, lines 1-32; col.28, lines 44-67]. Regarding claims 7 and 12, arginine is adjacent to proline (hydrophobic amino acid) (claim 7 of the ‘552 patent). The claim further recites peptide comprising two consecutive amino acids in natural configuration. Claims 1, 5-7, and 12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of copending Application No. 19329417 (hereinafter referred to as the ‘417 application). Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. Regarding claim 1, claim 1 of the ‘417 application recites a cyclic peptide PNG media_image7.png 72 241 media_image7.png Greyscale wherein Xn is a cargo moiety comprising a linker moiety, a therapeutic moiety, and a targeting moiety; m is 1; n is 3 (peptide of 8 amino acids) wherein each AA1, AA2, AA3, and AA4, are independently selected from an amino acid; AAz, at each instance, is independently selected from an amino acid; AAu is glutamine and the cargo moiety is conjugated to the side chain of AAu; 2 arginine amino acids with the remaining amino acids being an amino acid other than arginine; and at least two amino acids selected from AA1, AA2, AA3, AA4, and AAz are independently a hydrophobic amino acid selected from the recited Markush grouping. Regarding claim 5, all of the amino acids are in the natural stereoconfiguration (claim 8 of the ‘417 application). Regarding claim 6, the cargo moiety conjugated to the side chain of AAu comprises an 8-amino-3,6-dioxaoctanoic acid (claims 10 and 15 of the ‘417 application). Regarding claim 7, arginine is adjacent to glycine (hydrophobic amino acid) (claims 5-8, 11-13 of the ‘417 application). Regarding claim 12, at least two consecutive amino acids are in the natural stereoconfiguration (claim 16 of the ‘417 application). Claims 1 and 7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of copending Application No. 19329440 (hereinafter referred to as the ‘440 application). Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. Regarding claim 1, claim 1 of the ‘440 application recites a cyclic peptide of formula I-D comprising 8 amino acids wherein at least 2 amino acids are arginine, at least 3 are consecutive hydrophobic amino acids, and the cargo moiety is coupled to a side chain of the cyclic peptide. Regarding claim 7, arginine is adjacent to glycine (hydrophobic amino acid) (claims 7-10 of the ‘440 application). Claims 1, 5, 6, and 12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of copending Application No. 19329353 (hereinafter referred to as the ‘353 application). Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. Regarding claims 1 and 6, claims 1, 2, and 15 of the ‘353 application recite a cyclic peptide of formula wherein the peptide can contain 8 amino acids m =2, the peptide comprises 2 or 3 arginine, at least 3 hydrophobic amino acids (at least 2 of which are phenylalanine), a cargo moiety comprising a linker moiety, a therapeutic moiety, and a targeting moiety is coupled to a side chain of an amino acid of glutamine, and the linker moiety is 8-amino-3,6-dioxaoctanoic acid (miniPEG). Regarding claim 5, all of the amino acids are natural (claim 10 of the ‘353 application). Regarding claim 12, at least two consecutive amino acids are L amino acids (claim 8 of the ‘353 application). Claims 1, 6, and 7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of copending Application No. 19329423 (hereinafter referred to as the ‘423 application). Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. Regarding claim 1, claim 1 of the ‘423 application recites a cyclic peptide of formula I-D consisting of 8 amino acids, wherein a cargo moiety comprising a linker moiety, a therapeutic moiety, and a targeting moiety is coupled to a Glu side chain in the cyclic peptide, 2 amino acids are Arg, and at least one amino acid is an aromatic or non-aromatic hydrophobic amino acid. Regarding claim 6, the cargo moiety is conjugated to the side chain of Glu and comprises an 8-amino-3,6-dioxaoctanoic acid (claim 12 of the ‘423 application). Regarding claim 7, arginine is adjacent to glycine (hydrophobic amino acid) (claims 5-7 of the ‘423 application). Claims 1, 5-7, and 12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10, 12-14, and 16-19 of copending Application No. 19329427 (hereinafter referred to as the ‘427 application). Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. Regarding claim 1, claim 1 of the ‘427 application recites a cyclic peptide of formula I-D consisting of 8 amino acids, wherein a cargo moiety comprising a linker moiety, a therapeutic moiety, and a targeting moiety is coupled to a Glu side chain in the cyclic peptide, at least 2 amino acids are Arg, and at least one amino acid is an aromatic hydrophobic amino acid, all amino acids are natural (L), and Arg is adjacent to a hydrophobic amino acid. Regarding claim 5, all of the amino acids are in the natural stereoconfiguration (claim 1of the ‘427 application). Regarding claim 6, the cargo moiety comprises an 8-amino-3,6-dioxaoctanoic acid (claim 16 of the ‘427 application). Regarding claim 7, arginine is adjacent to glycine (hydrophobic amino acid) (claims 5-8, 11-13 of the ‘427 application). Regarding claim 12, at least two consecutive amino acids are in the natural stereoconfiguration (claim 1 of the ‘427 application). Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18734759 (hereinafter referred to as the ‘759 application). Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. Regarding claim 1, claim 1 of the ‘759 application recites a compound comprising a cell penetrating peptides of formula I, wherein 3 (or more) amino acids are arginine, and at least one is naphthylalanine, tryptophan, or phenylalanine (hydrophobic amino acid). The peptides can be comprise a linker attached to a cargo, and the moiety can comprise a therapeutic moiety and a targeting moiety (claims 3-10). The peptide is cyclic. Id. The peptide can contain 8 amino acids (e.g., formula Ia-3, II-a, IIb-2, IIc-3; claims 4-10). Claims 1, 5-7, and 12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 74, 82-83, and 88-89 of copending Application No. 18688096 (hereinafter referred to as the ‘096 application). Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. The ‘096 application claims a cyclic peptide attached to a therapeutic moiety via a linker (see claims 74, 83) wherein the CPP is a glutamine at the AAsc (site of attachment, see claim 88); two arginine residues (claim 83); lysine adjacent to ARG residues (claim 83) and wherein the linker is minipig (8-amino-3,6-dioxaoctanoic acid) and wherein all amino acids are in L-configuration. Relevant Art Not Relied Upon A cyclic peptide of SEQ ID NO:110 (elected species) appears to be free of the prior art. SEQ ID NO:110 has 86.4% identity with amino acid positions 45-52 of SEQ ID NO: 196994 of U.S. 2013/0333061. Pei et al (WO2015179691- earliest effective filing date 5/21/2014; cited in IDS filed 11/25/2025) discloses peptides of formula IIa-3 comprising a cyclic peptide of AA1-AA8 and a cargo (claim 22); formula IIb-c (claim 34). The peptide can contain 3 (or more arginine (claims 1, 37). The cargo moiety comprises a detectable moiety, a therapeutic moiety, a targeting moiety, or a combination thereof (claims 12, 39). The cargo moiety can comprise any cargo of interest, for example a linker moiety, a detectable moiety, a therapeutic moiety, a targeting moiety, and the like, or any combination thereof (p. 4). Peptide further include hydrophobic amino acids, e.g., Phe and Gln. The reference does not qualify as prior art under 102(a)(2) because the reference has the same two inventors, Pei and Qian. Qian (J Biochemistry 53:4034−4046 (2014) - cited in IDS filed 11/25/2025) teaches cyclo(FΦRRRRQ)K(Dex)-NH2 (see figure 1B, Table 1- peptide 2) wherein the peptide comprises 7 amino acids in the cyclic backbone, 4 Arg amino acids, a linker (lysine) and a therapeutic cargo dexamethasone (“Dex”). In contrast, the instantly claimed peptide contain 8 amino acids in the cyclic backbone, 2 Arg, and a targeting moiety. Qian (ACS Chem Biol 8:423-431 (2013) - cited in IDS filed 11/25/2025) - teaches cyclo(AFΦRRRRQ) (see Table 1- peptide 13) wherein the peptide comprises 8 amino acids in the cyclic backbone, including 4 Arg amino acids. In contrast, the instantly claimed peptide contain 8 amino acids in the cyclic backbone, 2 Arg (not 4 Arg), and a cargo moiety (linker, therapeutic moiety and targeting moiety). Conclusion No claims are allowed. Claims 1-12 are pending. Claims 2-4 and 8-11 are withdrawn. Claims 1, 5-7, and 12 are rejected. Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISTINA M HELLMAN whose telephone number is (571)272-2836. The examiner can normally be reached M-F 9:00 am-5:30 pm. 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, LIANKO GARYU can be reached at 571-270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /KRISTINA M HELLMAN/Examiner, Art Unit 1654