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 .
Election/Restrictions
Applicant’s election without traverse of the following species in the reply filed on May 13, 2026, is acknowledged:
Ac-PKKKRKV-miniPEG-K(cyclo(Ff-Nal-GrGrQ)-PEG12-OH, as disclosed in the specification in para. [0794]:
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further including a conjugated cargo (see, e.g. FIGS. 16 and 17).
The elected species was searched and is free of the prior art but is rejected for non-statutory double patenting. The search was extended and prior art was found that reads on claims 111, 120-121, and 135. The search was not extended further in accordance with MPEP § 803.02.
Claim 132 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.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 May 13, 2026.
Claim Objections
Claim 121 is objected to because the spacing implies that “wherein B is beta-alanine” is part of (ii) of the claim. To avoid confusion, the claim should be amended to include a hard return prior to “wherein” to clarify that this definition for B applies to both (i) and (ii).
Claims 124 and 132 are objected to because the symbol Φ is defined in the specification at [0091] but not in the claims. To avoid confusion, the claims should be amended to include the definition “wherein Φ is 3-(2-napthyl)-L-alanine”.
Claim 125 objected to because the symbol Nal is defined in the specification at [0091] but not in the claims. To avoid confusion, the claims should be amended to include the definition “wherein Nal is 3-(2-napthyl)-L-alanine”.
Claims 124, 125, and 132 are objected to because the use of lower case amino acid symbols is defined in the specification at [0091] but not in the claims. To avoid confusion, the claims should be amended to include the definition “wherein lower case amino acid symbols denote D-amino acids and upper case amino acid symbols denote L-amino acids”.
Claim Rejections - 35 USC § 112(a)
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.
Claim 135 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claim 135 is drawn to a method of using the claimed compounds to treat a disease. The claims include all cargos and all diseases. The specification does not disclose a single working example wherein the elected species Ac-PKKKRKV-miniPEG-K(cyclo(Ff-Nal-GrGrQ)-PEG12-OH is conjugated to a cargo and used to deliver said cargo to treat a disease. The elected species is not disclosed in the prior art. Given that the level of unpredictability in the pharmaceutical arts is high, one of ordinary skill would not be able to predict in the absence of even a single working example, whether the elected species could be used to treat any disease at all, let alone full genus of diseases. It is not even clear whether the elected species can be used to deliver a full range of cargo from oligonucleotides, peptides, and small molecules. There would be extraordinary burden to practice the full scope of the claimed invention.
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 111, 117, 119-124, 133, and 135 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.
In claim 111, the configuration of the cyclic peptide, exocyclic peptide, and linker is unclear. BRI of this limitation includes multiple, plausible constructions: 1) the linker connects to the cargo and also connects the cyclic peptide to the exocyclic peptide, 2) the cyclic peptide and exocyclic peptides are directly connected and the linker connects this combined peptide structure to the cargo, 3) the cyclic peptide and exocyclic peptides are connected by a different unrecited linker and the claimed linker connects this combined peptide structure to the cargo. The language is indefinite because it is not clear which construction is covered (e.g., because there is more than one reasonable interpretation of what construction is included in the claim). See MPEP § 2173.04. In addition, it is not clear how the connectivity is achieved.
Dependent claims 117, 119-124, 133, and 135 fail to remedy this issue and are likewise rejected.
Claim 120 is 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.
Regarding claim 120, the phrase "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 125 is 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.
The issue in this claim is illustrated with respect to the elected species but applies to all of the claimed compounds. From the compound name,
Ac-PKKKRKV-miniPEG-K(cyclo(Ff-Nal-GrGrQ)-PEG12-OH, it is not clear how the structure is formed. The confusion stems from the lysine and glutamine amino acids, each of which include a NH group. If both of these residues are present as implied in the claimed compound name, there would be an N-N bond. In contrast, the compound has a structure as disclosed in the specification in para. [0794]:
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wherein the side chain of lysine forms an amide bond with the side chain of glutamine. To avoid this issue, Applicant should amend the claims to depict the structure.
Furthermore, it is not clear how this structure can be present in its entirety and also be conjugated to a cargo via a bonding group M. It is not clear if the bonding group M is part of the species depicted above and if so, which atoms correspond to M.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 133 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to depend from a claim previously set forth. Claim 133 depends on claim 135.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 111, 120-121, and 135 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wissner.1
Claim Interpretation: BRI of the limitation “exocyclic peptide comprising from 2 to 10 amino acids” includes peptides limited to a length of 2 to 10 amino acid residues as well as those having a minimum length of 2 to 10 amino acid residues because the transitional phrase “comprising” is open and allows for additional unrecited elements (MPEP § 2111.03(I)).
Rejection: Wissner teaches (Figure 2):
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With respect to claim 111,
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is a cyclic peptide of Formula (IIb) wherein AAsc is glutamine, each of R2a and R2c is a side chain of arginine, and each n’ is 0.
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is a linker comprising a -(OCH2CH2)z’- subunit wherein z’ is 2.
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is a 182-residue polypeptide connected to a His-tag. The N-terminal sequence of SNAP is MDKDCEMKRTTL.2 This amino acid sequence comprises KR, which is a dipeptide comprising at least one arginine. The portion of the SNAP-His6 directly linked to the
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constitutes the cargo of claim 111. The segment of SNAP-His6 comprising KR constitutes the exocyclic peptide of claim 111.
Therefore, the compound of Wissner satisfies all of the limitations of claim 111.
Regarding claims 120-121, the exocyclic peptide comprises KR.
Regarding claim 135, Wissner teaches this compound in Tris buffer, which is a pharmaceutically-acceptable carrier (p. 1388, col 2).
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 111-114, 116-117, 119-125, 133, and 135 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of copending Application No. 18/506,057 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claims anticipate the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claims 111-112, 116-117, and 119-124, reference claim 18 recites the elected species Ac-PKKKRKV-miniPEG-K(cyclo(Ff-Nal-GrGrQ)-PEG12-OH and reference claim 9 requires that the compound is further conjugated to a cargo, specifically a therapeutic oligonucleotide, peptide, or small molecule.
Regarding claims 113-114 and 125, reference claims 3-4 require that the compound is attached to the cargo via
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or
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wherein t’ is 0-10.
Regarding claims 133 and 135, reference claim 21 recites a method of treating a disease comprising administering an effective amount of the compound.
Claims 111-114, 116-117, 119-125, 133, and 135 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 141-162 of copending Application No. 18/289,944 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claims anticipate the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claims 111-112, 116-117, and 119-124, reference claim 149 recites the elected species Ac-PKKKRKV-miniPEG-K(cyclo(Ff-Nal-GrGrQ)-PEG12-OH conjugated to an oligonucleotide cargo.
Regarding claims 113-114 and 125, reference claim 147 requires that the compound is attached to the cargo via
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or
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wherein t’ is 0-10.
Regarding claims 133 and 135, reference claim 156 recites a method of treating a disease comprising administering an effective amount of the compound.
Claims 111-114, 116-117, 119-125, 133, and 135 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 156-172 of copending Application No. 18/289,946 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claims anticipate the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claims 111-112, 116-117, and 119-124, reference claim 164 recites the elected species Ac-PKKKRKV-miniPEG-K(cyclo(Ff-Nal-GrGrQ)-PEG12-OH conjugated to an oligonucleotide cargo.
Regarding claims 113-114 and 125, reference claim 162 requires that the compound is attached to the cargo via
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or
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wherein t’ is 0-10.
Regarding claims 133 and 135, reference claim 172 recites a method of treating a disease comprising administering an effective amount of the compound.
Allowable Subject Matter
The following claims drafted by the examiner and considered to distinguish patentably over the art of record in this application, are presented to applicant for consideration. These claims would only be allowable if the non-statutory double patenting rejections made above are overcome.
136. A compound consisting of:
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wherein the -OH of the terminal carboxylic acid group is replaced by a bonding group M, which is linked to a cargo moiety.
137. The compound of claim 136, wherein the bonding group M comprises
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.
138. The compound of claim 136, wherein the bonding group M comprises
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wherein t’ is 0-10.
139. The compound of claim 136, wherein the cargo moiety is a therapeutic moiety selected from an oligonucleotide, a peptide, and a small molecule.
140. A pharmaceutical composition comprising the compound of claim 139 and a pharmaceutically-acceptable carrier.
The following is a statement of reasons for the indication of allowable subject matter: the closest prior art of Pei et al. (US 2019/0309020 A1) discloses cyclic cell-penetrating cyclic peptides and their use to deliver biologically active moieties into cells. The genus of cyclic peptides includes cyclic octapeptides comprising two or three arginines wherein the remaining amino acids are not arginine, and at least two amino acids are hydrophobic ([0005]-[0009]). The cyclic peptide is attached to a cargo, which can include a targeting moiety, a linker, and a therapeutic moiety ([0149]). Although the prior art genus includes the elected species, there is nothing in the reference to suggest the species or direct one of ordinary skill in the art to the species. For example, Table 4 of Pei et al. discloses specific cyclic peptides, none of which is the claimed cyclo(Ff-Nal-GrGrQ). In addition, Pei et al. nowhere discloses the targeting moiety PKKKRKV. In addition, Pei et al. nowhere discloses the specific linker or configuration between the cyclic peptide, targeting peptide, linker, and cargo present in the elected species.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA M MARCHETTI BRADLEY whose telephone number is (571)272-9044. The examiner can normally be reached Monday-Friday, 8:30 am - 5 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 G 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.
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CHRISTINA M MARCHETTI BRADLEY
Primary Examiner
Art Unit 1654
/CHRISTINA BRADLEY/Primary Examiner, Art Unit 1654
1 Wissner et al. Fluorescence Correlation Spectroscopy Reveals Efficient Cytosolic Delivery of Protein Cargo by Cell-Permeant Miniature Proteins. ACS Central Science 2018 4 (10), 1379-1393, DOI: 10.1021/acscentsci.8b00446; hereafter “Wissner”
2 The amino acid sequence of SNAP is reported by www.snapgene.com/plasmids/basic_cloning_vectors/SNAP-tag.
Prosecution Insights