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 .
Claim Status
Claims 1-26 are pending. Claims 23-26 are directed to a non-elected invention, and claims 2, 4-6, 8-9, or 14-21 are directed to non-elected species; claims 2, 4-6, 8-9, 14-21, 23-26 are withdrawn. Claims 1, 3, 7, 10-13, and 22 are presently considered.
Election/Restriction
Applicant’s election without traverse of Group I (products at claims 1-22) and the species of Example 14O and CPMB-0013 in the reply filed on 5/19/2026 is acknowledged.
Examiner notes that Applicant refers to multiple species (see, e.g., Reply filed 5/10/2026 at 3 at paragraph beginning with “Please note”), but the species election requires identification of a single, fully disclosed species (see requirement mailed 3/19/2026 at 3-4 and footnotes 1-2), not multiple species.
The originally elected species is understood to be CPMB-0013, which is has the structure of
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(see, e.g., Reply filed 5/19/2026 at 2; see also Spec. filed 10/18/2023 at Fig. 14O). The originally elected species is understood to comprise a 6-mer peptide sequence, namely KQKGKG2 (see, e.g., Spec. filed 10/18/2023 at Example 2 at lines 5-20). The originally elected species is understood to have three lysine residues, and each is conjugated to a GalNac moiety; the originally elected species is understood to have a single glutamine residue (Gln, not Glu), which is conjugated to
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. The originally elected species is understood to lack an agent per the statement that the compound “can be conjugated to an agent”, indicating that it is not yet conjugated to an “agent” (see, e.g., Reply filed 5/10/2026 at 3 at paragraph beginning with “Please note”).
The originally elected species is understood to read upon instant claims 1, 3, 7, 10-13, and 22. However, the originally elected species of CPMB-0013 does not read upon instant claims 2, 4-6, 8-9, or 14-21 as follows: The originally elected species does not read upon claims 2, 14-16, and 18-21 because claims 14-16 and 18-21 depend from claim 2, and claim 2 requires an “agent” to be present, but the originally elected species lacks an agent covalently bound to the cyclic peptide scaffold via a second linker. Rather, the originally elected species is understood to lack an agent per the statement in the response that CPMB-0013 “can be conjugated to an agent”, wherein “can be” indicates that CPMB-0013 is not yet conjugated to an “agent” (see, e.g., Reply filed 5/10/2026 at 3 at paragraph beginning with “Please note”). Therefore, the elected species does not read upon claims 2, 14-16, and 18-21. The originally elected species does not read upon claim 4-6, because claims 4-6 depend from claim 4, and require the presence of “at least one Glu residue” (i.e., “glutamic acid” or “glutamate”, “E”, which has a side chain of -(CH2)2-C(O)-OH), and the originally elected species lacks “at least one Glu”, and instead comprises a Gln residue (i.e., glutamine, Q, having a side chain of -(CH2)2-C(O)-NH2). Therefore, the elected species does not read upon claims 4-6. Claims 8 and 17 require the presence of SEQ ID NO: 5, 6, or 7, which each have a Glu residue. As explained above, the originally elected species lacks a Glu residue, and instead comprises a Gln residue. Therefore, the elected species does not read upon claims 8 and 17. Claim 9 requires a D-amino acid, but the originally elected species is understood to comprise only L-amino acids (see, e.g., Spec. filed 10/18/2023 at Example 2 at lines 5-20). Therefore, the elected species does not read upon claim 9. In sum, the originally elected species of CPMB-0013 is understood to read upon instant claims 1, 3, 7, 10-13, and 22; however, the originally elected species is not reasonably understood to read upon instant claims 2, 4-6, 8-9, or 14-21, which are directed to non-elected species.
Following extensive search and examination, the originally elected species3 has been deemed free of the prior art. Per MPEP § 803.02(III)
If the examiner determines that the elected species is allowable over the prior art, the examination of the Markush claim will be extended. If prior art is then found that anticipates or renders obvious the Markush claim with respect to a nonelected species, the Markush claim shall be rejected; claims to the nonelected species would still be held withdrawn from further consideration. The prior art search will not be extended unnecessarily to cover all nonelected species.
Accordingly, Examination was extended to a non-elected species, namely (1) CAS Reg No. 2855229-03-5; which was subsequently deemed free of the prior art. Examination was then subsequently extended to additional non-elected species, namely (2) CAS Reg No. 2855229-04-6; (3) CAS Reg No. 2855229-05-7; (4) CAS Reg No. 2855229-06-8; (5) CAS Reg No. 2855229-07-9; (6) CAS Reg No. 2855229-08-0; (7) CAS Reg No. 2855229-09-1; (8) CAS Reg No. 2855229-10-4; (9) CAS Reg No. 2855229-11-5; (10) CAS Reg No. 2855229-12-6; (11) CAS Reg No. 2855229-13-7; (12) CAS Reg No. 2855229-14-8; (13) CAS Reg No. 2855229-15-9; (14) CAS Reg No. 2855229-16-0; (15) CAS Reg No. 2855229-35-3; (16) CAS Reg No. 2855229-36-4; (17) CAS Reg No. 2855229-38-6; (18) CAS Reg No. 2855229-41-1; (19) CAS Reg No. 2855229-43-3; (20) CAS Reg No. 2855229-44-4; (21) CAS Reg No. 2855229-45-5; (22) CAS Reg No. 2855229-46-6; (23) CAS Reg No. 2855229-47-7; (23) CAS Reg No. 2855229-48-8; and (25) CAS Reg No. 2855229-42-2, which were all subsequently deemed free of the prior art (corresponding structures for each CAS Registry number are shown in the search notes).
Examination was then extended to the non-elected species of
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Following extensive search and examination, the non-elected species was deemed anticipated and/or obvious in view of the prior art as applied below. Per MPEP § 803.02(III), claims directed to other nonelected species have been withdrawn.
Claims 23-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 5/19/2026.
Claims 2, 4-6, 8-9, 14-21, 23-26 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 5/19/2026.
Claims 1, 3, 7, 10-13, and 22 are presently considered
Priority
The priority claim to PCT/CN2021/089305 (filed 4/23/2021) is acknowledged.
Information Disclosure Statement
The IDS filed 10/17/2024 and 5/19/2026 are each acknowledged and presently considered.
Claim Interpretation
For purposes of examination, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111. If Applicant disputes any interpretation, Applicant is invited to unambiguously identify any alleged misinterpretations or specialized definitions in the subsequent response to the instant action. Applicant is advised that a specialized definition should be properly supported and specifically identified (see, e.g., MPEP § 2111.01(IV), describing how Applicant may act as their own lexicographer).
Claim 1 is representative of the pending claim scope and are directed to products, namely “conjugates” that comprise (i) a 4 to 10-mer cyclic peptide scaffold comprising at least one Glu, Asp, Lys, or Arg residue, and (ii) “one or more N-acetylgalactosamine (GalNAc) moieties” bound to the cyclic peptide scaffold via a “first linker”. Applicable claim interpretations are provided below.
“Comprising” is an open-ended transitional term (see, e.g., MPEP § 2111.03(I)), wherein additional steps or components are not excluded. However, “‘[c]omprising’ is a term of art used in claim language which means that the named elements are essential” (see, e.g., id.; see also Genentech, Inc. v. Chiron Corp., 112 F.3d 495, 501, 42 USPQ2d 1608, 1613 (Fed. Cir. 1997)).
“Cyclic peptide scaffold” is interpreted consistent with the description set forth in the Specification at pages 7-8 (see, e.g., Spec. filed 10/18/2023 at 7 at line 20 to page 8 at line 19, Table 1 on page 8). The exact structure of the cyclic peptide is unlimited so long as it comprises 4-10 amino acid residues, and comprises at least one amino acid selected from the group consisting of Glu, Asp, Lys, and Arg. Note that the type and point of cyclization is not limited, and therefore the term is understood to encompass all types of cyclization, including intramolecular disulfide bonds. This raises the issue of whether or not exocyclic portions would constitute a “first linker” or count as one or more of the “4-10” amino acids of the cyclic peptide scaffold.
“Optional” limitations are interpreted per MPEP § 2111.04(I), which explains that “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure”.
“Amino acid residues” are not limited to proteinogenic amino acids, but are understood to be used to refer to any art-recognized amino acids, including β-amino acids (see, e.g., Spec. filed 10/18/2023 at 2 at lines 10-15, referring to SEQ ID NO: 7), D-amino acids (see, e.g., Spec. filed 10/18/2023 at 2 at lines 5-10), and any amino acids comprising the enumerated functional groups (see, e.g., Spec. filed 10/18/2023 at 7 at line 20 to page 8 at line 20).
“First linker” is structurally unlimited by molecular weight, length, or chemical composition (see, e.g., instant claim 1). Accordingly, the linker may be a peptide, alkyl chain, linear or branched, etc.
Claim 10 recites “CPS-001, CPS-002, CPS-003, and CPS-031, or a functional equivalent thereof” and “optionally wherein the cyclic peptide scaffold is CPS-001, CPS-002, CPS-003, or CPS-031”. The terms CPS-001, CPS-002, CPS-003, and CPS-031 are not art-recognized names for art-recognized structures, and the recitation at claim 10 is understood to be an attempt to import the data of Table 1 regarding SEQ ID NOs: 1-4 (see, e.g., Spec. filed 10/18/2023 at Table 1 at page 8).
Claim 10 recites “or a functional equivalent thereof”, but no structure/function relationship is provided on record reasonably informing artisans of the metes and bounds of what does or does not constitute a “functional equivalent” of such structures. For purposes of applying prior art, it is assumed that this language includes the originally elected species, which lacks a Glu residue, but instead has a Gln residue relative to CPS-001 (see, e.g., Spec. filed 10/18/2023 at Table 1 at page 8). If this is incorrect, then claim 10 would be withdrawn as directed to a non-elected species.
Claim 13 recites “the linker in Gal-1, Gal-2, Gal-3, Gal-4, or Gal-5” refers to an unknown linker by indirect reference to terms that are not art-recognized names for any art-recognized structures. The recitations are reasonably inferred to be an improper attempt to import the data of Table 2 regarding such compounds (see, e.g., Spec. filed 10/18/2023 at Table 2 at page 9). Furthermore, even if Table 2 were imported, the identification of what constitutes a “first linker” would be arbitrary.
“GalNAc moieties” (N-acetylgalactosamine moieties) are not structurally defined on record, but rather the closest description of record provides “exemplary” structures (see, e.g., Spec. filed 10/18/2023 at 8 at line 20 to page 9 at 13, Table 2 at page 9). All “GalNAc moieties” disclosed appear to comprise
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(see id. at Table 2 at page 9) or
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(see id. at Fig. 3); therefore, any structure comprising an N-acetylgalactosamine substructure having an NH-Ac is understood to be a “GalNAc moiety” for purposes of examination.
Additional claim interpretations are discussed below.
Specification
35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, requires the specification to be written in “full, clear, concise, and exact terms.” The specification is replete with terms which are not clear, concise and exact. The specification should be revised carefully in order to comply with 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112. Examples of some unclear, inexact or verbose terms used in the specification are:
The specification appears to repeatedly refer to structures comprising Glutamine (Q; Gln) incorrectly as comprising glutamic acid (E; Glu). For example, Table 1 refers to SEQ ID NOs: 1-4, and identifies that each comprises either “Glu(Cbz-Linker2)” or “DGlu(Cbz-Linker2)” (see, e.g., Spec. filed 10/18/2023 at Table 1 at page 8), but Figures 13A, 13B, 13C, and 13D show structures comprising a Gln(Cbz-Linker2) or D-Gln(Cbz-Linker2), without a Glu or D-Glu structure. This presence of Gln (Q) rather than Glu (E) in at least Compound 1 and Gal-1 is confirmed in the chemical names provided in the specification (see, e.g., Spec. filed 10/18/2023 at 24 at line 20-25 referring to a compound comprising “L-glutaminate”; at 25 at lines 10-15 referring to a compound comprising “L-glutamine” but then referring to it as “L-Fmoc-Glu”; at 26 at lines 5-10 referring to a compound comprising “L-glutaminyl”). Notably, the originally elected species is a 6-mer peptide sequence, namely KQKGKG4, and the CAS Registry No. identifies the correct amino acid sequence, which differs from the sequences of record (see, e.g., Spec. filed 10/18/2023 at Example 2 at lines 5-20).
This appears to be a systemic typographical error wherein the proper correction is recognizable in view of the proffered chemical names and chemical structures as Gln (Q, Glutamine) rather than Glu (E, Glutamic acid). Given the severity of the issue, wherein figures, sequence listings, and descriptions reasonably appear impacted,
A substitute specification not including the claims is required pursuant to 37 CFR 1.125(a) because the errors identified above appear to be systemic and pervasive in the originally filed disclosure.
A substitute specification must not contain new matter. The substitute specification must be submitted with markings showing all the changes relative to the immediate prior version of the specification of record. The text of any added subject matter must be shown by underlining the added text. The text of any deleted matter must be shown by strike-through except that double brackets placed before and after the deleted characters may be used to show deletion of five or fewer consecutive characters. The text of any deleted subject matter must be shown by being placed within double brackets if strike-through cannot be easily perceived. An accompanying clean version (without markings) and a statement that the substitute specification contains no new matter must also be supplied. Numbering the paragraphs of the specification of record is not considered a change that must be shown.
Sequence Listing
The instant disclosure is objected to for not complying with 37 C.F.R. 1.821 as detailed in MPEP §§ 2421–2424. Specifically, the instant application does not comply with 37 C.F.R. 1.821(b)-(e). The instant claims and/or disclosure contain references or disclosures of amino acid sequences that should be accompanied by a sequence listing and identified using "SEQ ID NOs” as prescribed (see, MPEP §§ 2421–2424). Specifically, the instant application discloses sequences at least at Figures 1, 2, 6, 13, and in the Specification filed 10/18/2023 at page 26 at lines 5-10, page 28 at lines 10-15, but these sequences do not correspond to instant SEQ ID NOs: 1-8 at least because instant SEQ ID NOs: 1-8 each contain Glu (E), but the sequences identified above contain Gln (Q).
Appropriate correction is required.
Drawings
The drawings are objected to because Figures 12, 14A, 14B, 14C, 14D, 14F, 14I, 14J, 14K, and 14M are not fully legible due to low resolution images. 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.
Claim Rejections
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, 3, 7, 10-13, and 22 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 is rendered indefinite in view of the phrase “wherein the cyclic peptide scaffold has 4-10, optionally 4-8amino acid residues, which comprise Glu, Asp, Lys, Arg, or a combination thereof” because it is unclear if “optionally” refers only to the range of “4-8”, or if optionally encompasses “4-8, amino acid residues which comprise Glu, Asp, Lys, Arg, or a combination thereof”. This raises substantial and material concerns regarding the metes and bounds of the claim scope because if the requirement for “Glu, Asp, Lys, Arg, or a combination thereof” is optional, then the claim scope is substantially broader than if the claim is limited to structures comprising “Glu, Asp, Lys, Arg, or a combination thereof”. Accordingly, the claim scope is indefinite. For purposes of applying prior art, the “optional” portion is reasonably inferred to optionally limit the range to “4-8” only; accordingly, the non-optional claim scope is understood to require a cyclic peptide scaffold having 4-10 amino acid residues. Applicant is advised that this issue could be overcome by simply removing optional language, which does not limit the claim scope per MPEP § 2111.04(I).
Claim 1 is rendered indefinite in view of the grouping of alternative limitations reciting “wherein the cyclic peptide scaffold has 4-10… amino acid residues, which comprise Glu, Asp, Lys, Arg, or a combination thereof”, because the grouping utilizes open-ended language (“comprises”) rather than closed language (“consists of”). Per MPEP § 2173.05(h), “If a Markush grouping requires a material selected from an open list of alternatives (e.g., selected from the group "comprising" or "consisting essentially of" the recited alternatives), the claim should generally be rejected under 35 U.S.C. 112(b) as indefinite because it is unclear what other alternatives are intended to be encompassed by the claim” (see, e.g., MPEP § 2173.05(h)(I)). For purposes of applying prior art, the pending claim scope is reasonably inferred to require a cyclic peptide scaffold having 4-10 amino acid residues, wherein the cyclic peptide “comprises at least one amino acid selected from the group consisting of Glu, Asp, Lys, and Arg”. This interpretation requires at least one amino acid from the closed group to be present, but permits additional amino acids, such as glycine to be present; this is a reasonable interpretation in view of the originally elected species and dependent claims 7 and 8.
Claim 10 recites and refers to “CPS-001, CPS-002, CPS-003, and CPS-031, or a functional equivalent thereof” and “optionally wherein the cyclic peptide scaffold is CPS-001, CPS-002, CPS-003, or CPS-031”, which render the claim scope indefinite because the terms CPS-001, CPS-002, CPS-003, and CPS-031 are not art-recognized names for any art-recognized structures, and therefore the metes and bounds of claim 10 is unknown. If Applicant is attempting to import the structures of Table 1 regarding SEQ ID NOs: 1-4 (see, e.g., Spec. filed 10/18/2023 at Table 1 at page 8), this is improper per MPEP § 2173.05(s), which explains that “Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Here, there is no exceptional circumstances appear to exist. Accordingly, the recitation of “CPS-001, CPS-002, CPS-003, and CPS-031” renders instant claim 10 indefinite. For purposes of applying prior art, claim 10 has been interpreted as reciting “SEQ ID NOs: 1-4” or “a functional equivalent thereof”.
Claim 10 recites “CPS-001, CPS-002, CPS-003, and CPS-031, or a functional equivalent thereof”, which renders the claim scope indefinite, because even assuming arguendo that “CPS-001, CPS-002, CPS-003, and CPS-031” refer to instant SEQ ID NOs: 1-4, it is unclear what structures do or do not constitute “a functional equivalent thereof” because no structure/function relationship is provided on record reasonably informing artisans of the metes and bounds of what does or does not constitute a “functional equivalent” of such structures. Per MPEP § 2173.05(g),
[T]he use of functional language in a claim may fail "to provide a clear-cut indication of the scope of the subject matter embraced by the claim" and thus be indefinite. In re Swinehart, 439 F.2d 210, 213 (CCPA 1971). For example, when claims merely recite a description of a problem to be solved or a function or result achieved by the invention, the boundaries of the claim scope may be unclear. . .
Here, the claims merely recite a description of a result to be achieved (i.e., “a functional equivalent”) by the invention rather than a description of the structure capable of achieving such a result. Therefore, the claims are indefinite per MPEP § 2173.05(g). This is reasonable because MPEP § 2173 identifies that the primary purpose of the requirement is to inform the public of the boundaries of what constitutes infringement of the patent, but here it is unclear what compounds do or do not infringe upon the scope of claim 10 as “functional equivalents”. Although it is reasonably assumed that the limitations of claim 10 are satisfied by the originally elected species, zero additional guidance or structure/function teachings are presented identifying any “functional equivalents” commensurate in scope with instant claim 10. Notably, the courts have stated that
Regardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to the subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.” University of Rochester v. G.D. Searle Co., 69 USPQ2d 1886 1984 (CAFC 2004) (emphasis added).
Accordingly, because it is unclear what compounds do or do not satisfy the functional limitations of claim 10, and an artisan would be unable to identify infringing from non-infringing compounds, claim 10 is rejected as indefinite. For purposes of applying prior art, claim 13 has been interpreted as reading upon at least the originally elected species. Further examination of claim 19 in view of the prior art is presently precluded.
Claim 12 is rendered indefinite in view of the grouping of alternative limitations reciting “wherein the 3-8 atoms comprise C, O, or a combination thereof”, because the grouping utilizes open-ended language (“comprises”) rather than closed language (“consists of”). Per MPEP § 2173.05(h), “If a Markush grouping requires a material selected from an open list of alternatives (e.g., selected from the group "comprising" or "consisting essentially of" the recited alternatives), the claim should generally be rejected under 35 U.S.C. 112(b) as indefinite because it is unclear what other alternatives are intended to be encompassed by the claim” (see, e.g., MPEP § 2173.05(h)(I)). For purposes of applying prior art, the pending claim scope is reasonably inferred to require “wherein the 3-8 atoms comprise at least one atom selected from the group consisting of C and O”. This interpretation is reasonable because it permits the presence of hydrogen atoms, which are present in the exemplified linkers of record.
Claim 13 recites “the linker in Gal-1, Gal-2, Gal-3, Gal-4, or Gal-5”, which render the claim scope indefinite because the terms Gal-1, Gal-2, Gal-3, Gal-4, or Gal-5 are not art-recognized names for any art-recognized structures, and therefore “the linker” refers to an unknown structure lacking antecedent basis in the claim set, and therefore a structure having indefinite metes and bounds. If Applicant is attempting to import the structures of Table 2 in whole or in part (see, e.g., Spec. filed 10/18/2023 at Table 2 at page 9), this is improper per MPEP § 2173.05(s), which explains that “Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Here, there is no exceptional circumstances appear to exist. Accordingly, the recitation of “the linker in Gal-1, Gal-2, Gal-3, Gal-4, or Gal-5” renders instant claim 13 indefinite. For purposes of applying prior art, claim 13 has been interpreted as reading upon at least the originally elected species. Further examination of claim 13 in view of the prior art is presently precluded.
Claims 3, 7, 10-13, and 22 depend directly or indirectly from an indefinite base claim, but fail to clarify or rectify the indefiniteness of the base claim. Accordingly, these claims are rejected for the reasons applied to the base claim, above.
Accordingly, claims 1, 3, 7, 10-13, and 22 are rejected.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
[Prior Art Rejection 01]
Claims 1, 3, 7, 11-12, and 22 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being clearly anticipated by US 9856294 (Jan. 2, 2018; Ferrand et al.)
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section above, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
US’294 pertains to cyclodecapeptide compounds for use as drugs (see, e.g., US’294 at title, abs). Regarding instant claims 1, 3, 7, and 11-12, US’294 reduces to practice
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(see, e.g., US’294 at cols 13-14 at lines 1-40, col. 15 at lines 10-42). These two structures satisfy the instant claims because the structure is a bicyclic decapeptide comprising one or more lysine residues conjugated to GalNac moieties via a first linker, wherein the first linker comprise 3-8 atoms (e.g., -C(O)-(CH)=N-), wherein the atoms comprise at least one atom from the group consisting of C and O, and wherein the bicyclic structure comprises a cyclic hexapeptide structure and therefore “has 6 amino acids” (compare instant claims 1, 3, 7, and 11-12 with US’294 at cols 13-14 at lines 1-40). Regarding instant claim 22, and a pharmaceutically acceptable excipient, an artisan would at once envisage the disclosed compounds in combination with a pharmaceutically acceptable excipient (see, e.g., US’294 at claims 1-2, 4, and 12).
Accordingly, claims 1, 3, 7, 11-12, and 22 are anticipated by the prior art.
[Prior Art Rejection 02]
Claims 1, 7, 11-12, and 22 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being clearly anticipated by US 2023/0398224 (filed on Feb. 7, 2020).
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section above, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
Regarding instant claims 1, 7, and 11-12, US’224 discloses
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(see, e.g., US’224 at col. 106-108, claims 45- 50; see esp. id. at claim 50; see also US’224 at ¶¶[0464]-[0466]). These structures satisfy the pending claims as follows: the structures are cyclic peptides having between 4 and 10 amino acids, wherein the cyclic peptides comprise at least one Lys residue, which is conjugated to a “GalNAc moiety” via a linkage, wherein the linkage may be arbitrarily deemed to comprise a first linker, a second linker, a third linker, etc., etc., and wherein a first linker may arbitrarily be defined as including 3-8 atoms comprising Carbon, oxygen, and hydrogen atoms (see, e.g., US’224 at col. 106-108; see also US’224 at ¶¶[0464]-[0466]). Regarding instant claim 22, and a pharmaceutically acceptable excipient, an artisan would at once envisage the disclosed compounds in combination with a pharmaceutically acceptable excipient (see, e.g., US’224 at title, abs, ¶[0005], claims 45-50, noting that the purpose of the compounds is for pharmaceutical applications).
Claims 1, 7, 11-12, and 22 are rejected
[Prior Art Rejection 03]
Claims 1, 3, 7, and 22 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being clearly anticipated by Chen et al9.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section above, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
Regarding instant claims 1, 3, 7, and 22, Chen discloses
PNG
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285
221
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Greyscale
(see, e.g., Chen at Scheme 4 on 1971). The cyclic peptide comprises a lysine residue, six amino acids, and the cyclic peptide is conjugated to a GalNAc via a linker comprising a bond or otherwise oxygen (see, e.g., Chen at Scheme 4 on 1971 at structure 7), wherein the structure is in a pharmaceutically acceptable carrier, namely MesNa and PBS (see id).
Accordingly, claims 1, 3, 7, and 22 are rejected.
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.
[Prior Art Rejection 04]
Claims 1, 3, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over US2012/0165393 in view of Danielsen et al.10, Qian et al.11, and Song et al.12.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section above, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
Regarding instant claims 1, 3, and 22, US’393 teaches and discloses a delivery system for siRNAs into liver cells, wherein the delivery system comprises
RNAi-A+Melittin-(L-Gal)x
(see, e.g., US’393 at claims 1-4, 6-8, 10-14, and 19; see also id. at ¶¶[0069], [0165]), wherein a cell penetrating peptide (i.e., a melittin) is conjugated via a linker “L” to a “Gal” (i.e., an ASGPr ligand), which may be GalNac, and wherein the composition may be optionally conjugated to RNAi via a second linker, and wherein “A” may be a “galactose cluster” consisting of an N-acetylgalactosamine trimer (see, e.g., US’393 at claims 1-4, 6-8, 10-14, and 19; see also id. at ¶[0165]). Regarding instant claim 22, US’393 explicitly directs artisan to formulate such compounds with pharmaceutically acceptable carriers (see, e.g., US’393 at claims 1 and 18).
The primary reference differs from the pending claim scope as follows: US’393 differs from the instant claim scope because US’393 utilizes melittin, rather than a cyclic cell-penetrating peptide. Therefore, the relevant issue is whether or not it would be obvious to substitute melittin peptides with cyclic cell penetrating peptides.
Melittin belongs to the class of cell penetrating peptides: melittin is identified as a “delivery peptide” that “provide[s] membrane penetration function” to the embodiments of US’393 (see, e.g., US’393 at title, abs). Notably, an artisan would readily appreciate that melittin peptides as used and claimed by US’393 belonged to an art-recognized class of compounds, namely cell-penetrating peptides (see, e.g., Danielsen at title, abs). An artisan would readily appreciate that cell penetrating peptide have “the ability to interact with cell membranes in order to enter cells and/or deliver cargo” and act as “permeation enhancers” to facilitate the delivery of “proteins or DNA” (see, e.g., Danielsen at abs).
The class of cell penetrating peptides included cyclic cell-penetrating peptides: Song and Qian pertain to art-recognized cyclic cell-penetrating peptides, including 6-mers comprising at least one arginine (see, e.g., Song at title, abs, Fig. 1 on 2085, structures on 2086, 2087 at col I at 2nd ¶, 2088 at col II at 2nd full ¶.; compare id. with instant claim 3). Similarly, Qian discloses cyclic cell penetrating peptides (see, e.g., Qian at title, abs), including 6-mers and 7-mers (see, e.g., Qian at Table 1 on 2602, Table 1 on 2602, Table 2 on 2604, 2608-2609 at § Discussion, discussing the advantages of small cyclic cell penetrating peptides; compare id. with instant claim 3). Accordingly, the class of cell penetrating peptides was known to include both melittin and cyclic peptides.
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s):
The claimed invention is the simple substitution of one known and art-recognized cell-penetrating peptide (e.g., a cyclic CPP as disclosed by Song or Qian) for another known and art-recognized cell penetrating peptide (e.g., melittin as used in the primary reference), wherein such compounds were art-recognized functional equivalents and usable for the same purpose, namely to facilitate delivery of agents into cells, and therefore such simple substitution would yield predictable results, namely compounds as taught and claimed by the primary reference, but utilizing cyclic cell penetrating peptides in place of the cell penetrating peptide of melittin, wherein the compounds would predictably retain the functionality and applications disclosed by the primary reference (see MPEP §§ 2143(I)(B), 2144.06(II)).
No evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record to date.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to substitute a known one known peptide for another in a known arrangement, wherein the peptide functionality in combination is merely expected to be the same as the peptides functionality used separately.
Accordingly, claims 1, 3, and 22 are rejected.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
US2020/0318113A1 pertains to cyclic peptides conjugated to siRNAs (see, e.g., US’113 at title, abs, claims, passim).
US 20140080759 claims and discloses cyclic peptides in combination with, but not conjugated to glycosaminoglycans such as GalNAc (see, e.g., US’759 at claims 1-3, 12, ¶[0136]-[0140]).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RANDALL L BEANE whose telephone number is (571)270-3457. The examiner can normally be reached Mon.-Fri., 7 AM to 2 PM ET.
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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/RANDALL L BEANE/ Primary Examiner, Art Unit 1654
1 This is understood to be CAS Number 2855229-39-7; cyclic QKGKGK
2 The structure is incorrectly identified as comprising a Glu (E) moiety. However, the structure shown comprises a Gln (Q) moiety (i.e., a glutamic acid is not present, but rather the residue is a glutamine).
3 This is understood to be CAS Number 2855229-39-7; cyclic QKGKGK
4 The structure is incorrectly identified as comprising a Glu (E) moiety. However, the structure shown comprises a Gln (Q) moiety (i.e., a glutamic acid is not present, but rather the residue is a glutamine).
5 This structure is understood to correspond to CAS Reg No. 1260524-11-5; see search notes.
6 CAS Reg. No. 2684286-64-2
7 CAS Reg. No. 2684286-66-4
8 CAS Reg. No. 2684286-67-5
9 Chen et al., A route to cyclic peptides and glycopeptides by native chemical ligation using in situ derived thioesters, Tetrahedron Letters, Volume 47, Issue 12, 2006, Pages 1969-1972, ISSN 0040-4039, https://doi.org/10.1016/j.tetlet.2006.01.077; cited in IDS filed 5/19/2026 as cite no. 2.
10 See, e.g., Danielsen et al., Impact of cell-penetrating peptides (CPPs) melittin and Hiv-1 Tat on the enterocyte brush border using a mucosal explant system. Biochim Biophys Acta Biomembr. 2018 Aug;1860(8):1589-1599. doi: 10.1016/j.bbamem.2018.05.015. Epub 2018 May 29. PMID: 29856994; cited in previous action.
11 Qian et al., Discovery and Mechanism of Highly Efficient Cyclic Cell-Penetrating Peptides. Biochemistry. 2016 May 10;55(18):2601-12. doi: 10.1021/acs.biochem.6b00226. Epub 2016 Apr 28. PMID: 27089101; PMCID: PMC8562596; cited in previous action.
12 Song et al., Cyclic Cell-Penetrating Peptides with Single Hydrophobic Groups. Chembiochem. 2019 Aug 16;20(16):2085-2088. doi: 10.1002/cbic.201900370. Epub 2019 Jul 24. PMID: 31298779; PMCID: PMC6752721; cited in previous action.
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