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
In response to the restriction requirement dated 27 October, 2025, Applicant elects, without traverse: the first peptide having SEQ ID NO: 1; the gene-binding region consisting of 1-4 residue peptides containing a lysine (K) residue; the second peptide having SEQ ID NO: 2; the first linker Ahx2; and the second linker Ahx2. Claim 8 is withdrawn. Applicant’s election in the reply filed on 15 December 2025 is acknowledged.
Claims 1-7, 9-22, are hereby examined on the merits. Claim 8 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Priority
Acknowledgement is made of Applicant’s claim for foreign priority to 10-2022-0034890, filed 03/21/2022; and 10-2023-0023099, filed 02/21/2023 under 35 U.S.C. 119(a)-(d).
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/11/2025 complies with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
The specification filed on 06/30/2023 does not recite appropriate sequence identifiers in the form of SEQ ID numbers. For example, please see: page 20, line 1; page 38, line 20; page 40, line 12; page 41, line 27. The sequences recited in the specification must include SEQ ID numbers to properly identify the sequences. Appropriate correction is required.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Objections
Claims 1 and 7 are objected to because of the following informalities: Examiner respectfully requests the addition of “:” after “NO” in the sequence identifiers. Appropriate correction is required.
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 1-7 and 9-22 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.
Independent claim 1, is directed to a fusion peptide consisting of a gene-binding region (b). The gene-binding region (b) is directed to “1-4 residue peptides” that can be interpreted as several 1-4 residue peptides which can vary in length and sequence, and ambiguity arises. Claim 1 is indefinite as it is unclear as to what the limitation “1-4 residue peptides” is referring to.
For examination, the claim will be interpreted to be a 1-4 residue peptide.
Claims 2-7 and 9-22 which depend on claim 1, are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as these claims incorporate by dependency the indefiniteness of claim 1.
Claim 3 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 term “ provide dynamic plasticity by forming sliding, scissoring or bending” in claim 3 is a relative term which renders the claim indefinite. The terms “dynamic plasticity”, “bending” and “scissoring” is not defined by the claim. The embodiments of the specification recite “dynamic plasticity” as “may be provided because electrostatic interaction is formed between …” (see page 15, line 24) but does not provide a standard for ascertaining the requisite degree. Consequently, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The claim limitation does not clearly set forth the metes and bounds of the fusion peptide.
Claim 5 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. Claim 5 recites the limitation, "the glutamic acid" of the first peptide and “the lysine” of the second peptide. The first peptide comprises 4 glutamic acid residues and the second peptide comprises 4 lysine residues. It is unclear which specific glutamic acid or lysine residues are involved in the interaction. There is insufficient antecedent basis for this limitation in the claim. The antecedent basis rejection is overcome by the Applicant by pointing to the amino acid location within the sequence of the first and second peptide.
Claim 10 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.
Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). The term “base-pairing” in claim 10 is used by the claim to mean “binding between gene-binding region (b) and nucleic acid,” while the accepted meaning is, “base pair, in molecular biology, two complementary nitrogenous molecules that are connected by hydrogen bonds. Base pairs are found in double-stranded DNA and RNA, where the bonds between them connect the two strands, making the double-stranded structures possible. Base pairs themselves are formed from bases, which are complementary nitrogen-rich organic compounds known as purines or pyrimidines. According to Watson-Crick base-pairing, which forms the basis for the helical configuration of double-stranded DNA, DNA contains four bases: the two purines adenine (A) and guanine (G) and the two pyrimidines cytosine (C) and thymine (T). Within the DNA molecule, A bonds only with T and C bonds only with G. In RNA, thymine is replaced by uracil (U). Non-Watson-Crick base-pairing models display alternative hydrogen-bonding patterns; examples are Hoogsteen base pairs, which are A-T or C-G analogues.” (source: Britannica).
The term is indefinite because the specification does not clearly redefine the term.
Claim 20 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 term ‘a self-assembled monolayer’ is an indefinite term because it is unclear what the monolayer refers to. For examination, the monolayer is interpreted as the peptide-molecule conjugate.
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.
Claim(s) 1, 2, 3, 5, 7, 11, 12, 16 are rejected under 35 U.S.C. 102 (a)(1) and 35 U.S.C. 102 (a)(2) as being anticipated by Michigami et al., hereinafter Michigami (Michigami M, et al., (2021) A “ligand-targeting” peptide-drug conjugate: Targeted intracellular drug delivery by VEGF-binding helix-loop-helix peptides via receptor-mediated endocytosis. PLoS ONE 16(2)).
Michigami teaches helix-loop-helix structures, termed “molecularly targeting HLH peptide”, designed based on the structural properties of intramolecular antiparallel coiled coils composed of three structural regions: the N-terminal α-helix, the C-terminal α-helix, and the connecting loop (see Fig 2a). In both helical regions, uncharged leucine residues are incorporated into interhelical positions to dimerize α-helices via hydrophobic interactions (see Results and Discussion, 1st paragraph).
Claim 1 is directed to a fusion peptide consisting of a first peptide of SEQ ID NO: 1 (X₁-E-L-X₂-X3-L-E-X4-E-L-X5-X6-L-E), a gene-binding region of 1-4 residue peptide containing a lysine residue and a second peptide of SEQ ID NO: 2 (K-L-X7-X8-L-K-X9-K-L-X10-X11-L-K-X12). The first linker binds SEQ ID NO: 1 and gene-binding region and the second linker binds the gene-binding region and SEQ ID NO: 2.
The HLH peptide of Michigami, (CAAELAALEAELAALEGX1X1X1X1X1X1X1X1X1GKLX2X2LKX2KLX2X2LKX2AC), wherein X is any amino acid, is a 100% sequence match to the fusion peptide as claimed (see Table 1, page 5). The highlighted sequence of Michigami shows the sequence match with the fusion peptide of the instant claim. Michigami teaches a 4-residue peptide sequence (PWXG; where ‘X’ is any amino acid) in the loop region that plays a role in the binding to VEGF (see page 3, 1st paragraph). As shown in Fig 2a, the first peptide is linked to the connecting loop and the second peptide is linked to the connecting loop. Thus, the HLH peptide of Michigami, anticipates the fusion peptide of claim 1.
Regarding claim 2, Michigami teaches HLH peptides with N-terminal α-helix, the C-terminal α-helix, and the connecting loop. The connecting loop sequence is in the center, linked to the N-terminal α-helix, the C-terminal α-helix (see Table 1 sequence; Fig 2a; see Results and discussion section ‘screening of a phage-displayed HLH peptide library, line 3).
Claim 3 is directed to the fusion peptide of claim 1 wherein the first and second peptide provide dynamic plasticity. Michigami recites a HLH structure that is substantially identical to the fusion peptide as instantly claimed. Therefore, the claimed properties or functions are presumed to be inherent. Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). (See MPEP § 2112.01 (I)).
Regarding claims 5 and 7, Michigami teaches a HLH peptide with 100% sequence identity to the fusion peptide as instantly claimed. The formation of a hydrophobic core inside the two-helix bundle is considered a driving force for folding into the HLH motif (see paragraph ‘Structure-binding relationship and proteolytic resistance of HLH peptide M49’, last three lines). Michigami teaches that the uncharged leucine residues incorporated into interhelical positions dimerize the α-helices via hydrophobic interactions (see ‘Screening of a phage-displayed HLH peptide library’, line 4). Regarding the limitation in claim 5 ‘wherein electrostatic interaction is formed between the glutamic acid (E) of the first peptide and the (K) of the second peptide, Michigami teaches a substantially identical peptide and therefore anticipates the limitation of the claim (see MPEP § 2112.01 (I)).
Regarding claim 7, the limitation wherein ‘fusion peptide has a hairpin structure’, embodiments of the specification does not disclose a special definition of a ‘hairpin structure’. Under a broadest reasonable interpretation (BRI), words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. In re Zletz, 893 F.2d 319, 321, 13 USPQ2d 1320, 1322 (Fed. Cir. 1989) (discussed below); Chef America, Inc. v. Lamb-Weston, Inc., 358 F.3d 1371, 1372, 69 USPQ2d 1857 (Fed. Cir. 2004). The plain meaning of a term means the ordinary and customary meaning given to the term by those of ordinary skill in the art at the relevant time.
The ordinary and customary meaning of a “hairpin structure” in the art, before the effectively filed date of the claimed invention, is the fundamental process of folding in two linear peptides that form hairpin structures, having a stabilizing hydrophobic cluster connected by loops of differing lengths (See Abstract; R. Brian Dyer et al., The Mechanism of β-Hairpin Formation†Biochemistry 2004 43 (36), 11560-11566).
Michigami teaches two helices connected by a loop region and that interhelical positions in the α-helices dimerize via hydrophobic interactions (see ‘Screening of a phage-displayed HLH peptide library’, line 4). Although Michigami does not recite the term “hairpin” for the HLH peptide, the sequence and structure of Michigami anticipate the limitation of claim 7.
Claims 11, 12 and 16 are directed to a peptide molecule conjugate wherein a hydrophilic conjugate is bound to at least one or both terminals of the first peptide and the second peptide of the fusion peptide.
Claim 16 is directed to the peptide molecule conjugate for nucleic acid delivery.
Regarding claims 11 and 12, as noted in Michigami, amide resin is bound to the C-terminal helix of the HLH peptide (see Supplementary Fig S7). Michigami teaches the screening of phage-displayed HLH peptides (for VEGF-A binding specificity) against biotinylated VEGF-A and bound phages captured using streptavidin-coated magnetic beads (see Results and discussion section ‘screening of a phage-displayed HLH peptide library).
Regarding claim 16, the term “for nucleic acid delivery” is interpreted by the examiner as intended use. If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020) (see MPEP § 2111. 02 (II)) As previously noted, where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). (See MPEP § 2112.01 (I)).
Michigami teaches peptide molecule conjugate which anticipates the limitations in claims 11, 12 and 16.
Claim Rejections - 35 USC § 103
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 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.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Michigami et al., hereinafter Michigami (Michigami M, et al., (2021) A “ligand-targeting” peptide-drug conjugate: Targeted intracellular drug delivery by VEGF-binding helix-loop-helix peptides via receptor-mediated endocytosis. PLoS ONE 16(2)) in view of Markowska, A et al., hereinafter AM (Markowska, A et al. (2021) The importance of 6-aminohexanoic acid as a hydrophobic, flexible structural element. Int. J. Mol. Sci. 22, 12111).
Claim 4 is directed to the fusion peptide of claim 1 wherein the first and second linker is Ahx2.
As noted, in reply to an election requirement on 15 December 2025, applicant elected the first linker Ahx2; and the second linker Ahx2.
Michigami teaches the HLH peptide (CAAELAALEAELAALEGX1X1X1X1X1X1X1X1X1GKLX2X2LKX2KLX2X2LKX2AC), wherein X is any amino acid. The peptide is a 100% sequence match to the fusion peptide as claimed (see Table 1, page 5). The highlighted sequence of Michigami shows the sequence match with the fusion peptide of the instant claim. Michigami teaches a 4-residue peptide sequence (PWXG; where ‘X’ is any amino acid) in the loop region that plays a role in the binding to VEGF (see page 3, 1st paragraph). As shown in Fig 2a, the first peptide is linked to the connecting loop and the second peptide is linked to the connecting loop.
Michigami does not teach the linker is Ahx2.
AM teaches Ahx as a linker (pages 6-10) and of introducing Ahx into the structure of peptides with biological activity. Table 2 correlates Ahx introduction in peptides and corresponding biological activity benefits. AM teaches that the methylene groups in the Ahx residue provide additional hydrophobic interaction with DNA. AM teaches that the insertion of Ahx in the structure of a peptide prevents enzyme hydrolysis in vivo and influences biological activity (see page 6, 4th paragraph). AM teaches that Ahx as linkers is significantly less cytotoxic to the 293 tested human embryonic kidney cells (see page 7, 3rd paragraph). AM teaches that one option for improving the biological properties of the compounds is to use an Ahx in place of a peptide fragment to design synthetic peptide/protein mimics (see page 8, 2nd paragraph).
Obviousness can be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so. In re Kahn, 441 F.3d 977, 986, 78 USPQ2d 1329, 1335 (Fed. Cir. 2006) (discussing rationale underlying the motivation-suggestion-teaching test as a guard against using hindsight in an obviousness analysis). Consequently, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the peptide of Michigami, which corresponds to 100% sequence identity of the fusion peptide in the instant application, and introduce Ahx2 linkers in the instant application. One motivated to do so would have a reasonable expectation of success as Ahx linkers demonstrate improved biological activity (Table 2) and insertion of Ahx in the structure of a peptide prevents enzyme hydrolysis in vivo. Thus, one would have recognized that applying the teaching of Michigami to the method of AM, would have yielded predictable results and improved the biological suitability of the fusion peptide (See MPEP § 2143 I(A)(D)).
Claims 6, 9, 10, 15, 17, 18, 20 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Michigami et al., hereinafter Michigami (Michigami M, et al., (2021) A “ligand-targeting” peptide-drug conjugate: Targeted intracellular drug delivery by VEGF-binding helix-loop-helix peptides via receptor-mediated endocytosis. PLoS ONE 16(2)) in view of Marya Ahmed, hereinafter Marya (Marya Ahmed (2017) Peptides, polypeptides and peptide-polymer hybrids as nucleic acid carriers Biomater. Sci. 5, 2188).
Claim 6 is directed to the fusion protein of claim 1 wherein the gene-binding region is covalently bonded to adenine, guanine, cytosine, thymine or uracil.
Claim 9 is directed to the fusion protein of claim 1 wherein the gene-binding region binds a negatively charged target.
Claim 10 is directed to the fusion peptide of claim 1 wherein nucleic acid binds at the gene-binding region.
Claim 15 is directed to the peptide-molecule conjugate wherein the peptide-molecule conjugate surrounds the nucleic acid molecule.
Claim 17 is directed to the peptide-molecule conjugate of claim 16 wherein the peptide-molecule conjugate binds DNA or RNA.
Claim 18 is directed to the peptide-molecule conjugate further comprising one or more selected from the group consisting of amantadine, ammonium chloride, polyethylenimine and chroloquine.
Claim 20 is directed to the formation of a nanostructure.
Claim 21 is directed to a nanotube.
Michigami teaches the HLH peptide which is a 100% sequence match to the fusion peptide as claimed (see Table 1, page 5). Michigami teaches a 4-residue peptide sequence in the loop region (PWXG; where ‘X’ is any amino acid) that plays a role in the binding to VEGF (see page 3, 1st paragraph). The variable sequence in the loop region of HLH peptides is screened for VEGF-A binding specificity against biotinylated VEGF-A and bound phages captured using streptavidin-coated magnetic beads (see Results and discussion section ‘screening of a phage-displayed HLH peptide library). Michigami teaches amide resin is bound to the C-terminal helix of the HLH peptide (see Supplementary Fig S7).
Michigami does not teach the binding of nucleic acid or negatively charged target or the binding of adenine, guanine, cytosine, thymine or uracil to the gene binding region.
Regarding claims 6, 9 ,10, 17, Marya teaches that amphipathic peptides are known to traverse the cell membrane for macromolecule delivery. Due to the inherent DNA condensation efficacies, amphipathic peptides are potential gene delivery vectors, which lack the immunological and toxic properties of virus-mediated gene delivery (see page 2111, introduction). Marya teaches that lysine and arginine are among the first amino acid-based peptides and the most commonly used gene therapy agents since the 1900s. Tat mimicking cationic peptides such as oligo-arginine and oligo-lysine readily condenses DNA and produces stable complex under physiological conditions (see page 2193, section ‘cationic peptides’). Marya teaches that gene delivery efficacies of linear oligo-arginine and oligo-lysine peptides revealed that oligo-lysine peptides are superior gene transfection agents to their oligo-arginine counterparts. In Table 1, Marya teaches a list of amino acid sequences of peptides as gene delivery carriers. Marya teaches the incorporation of hydrophobic moieties into the string of cationic amino acids to improve gene expression of cationic peptides by reducing their toxicities, by enhancing their membrane perturbation efficacies, and by increasing cellular uptake due to non-specific interactions of hydrophobic residues with the plasma membrane. Marya teaches that simplified cationic amphipathic peptides comprising lysine (K) and leucine (L) repeats were among the first synthetic secondary amphipathic peptides exhibiting the α-helical conformation and membrane penetrating activities as a function of peptide chain length (see page 2194, section ‘amphipathic peptides’). In Figure 8, Marya teaches the binding of lysine-containing peptides to negatively charged DNA. Marya teaches that bioactive peptide on synthetic scaffolds, such as polymers, proteins, lipids, nanoparticles is a strategy to produce physiologically stable and efficient nucleic acid therapeutics (see peptide-polymer hybrids, page 2200).
Regarding claim, 15 and 20, Marya teaches nanostructures of a nucleic acid core and K21 peptide, to mediate DNA condensation (see Fig 8). Marya teaches peptide-DNA complexes in an amphiphilic PEG-PLGA layer produces stable nano-complexes for efficient delivery (see page 2201, column 2).
Regarding claim 18, Marya teaches chloroquine (see page 2189, column 2) as a required agent for endosomal buffering to aid gene expression of peptide sequences and their oligomeric analogs (see Fig 1b).
Regarding claim 21, embodiments of the instant specification disclose that SAB-g₃/mRNA nanostructures are formed along the mRNA nanofiber. Therefore, the SAB-g₃/mRNA nanostructure is also referred to as an SAB nanotube (see page 36, lines 13-16).
The structure taught in Marya is a nanostructure and is formed along the siRNA as shown in Figure 8, meeting the limitations of the claim.
Marya teaches that one of the major problems with cationic peptide-based gene delivery vectors is the complexation of nucleic acids with cationic or cationic amphipathic peptides, which neutralizes the net cationic character and abolishes the cell penetration. Marya teaches that Lysine-rich regions when complexed with amphipathic peptides, condenses siRNA to produce discrete nanoparticles and mediate a ~100 fold superior gene knock down efficacy in vitro (see page 2200, column 1, 2nd paragraph).
Obviousness can be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so. In re Kahn, 441 F.3d 977, 986, 78 USPQ2d 1329, 1335 (Fed. Cir. 2006) (discussing rationale underlying the motivation-suggestion-teaching test as a guard against using hindsight in an obviousness analysis). Consequently, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the loop region of Michigami, with a peptide sequence containing a lysine residue, as taught in Marya, for binding a negatively charged target or nucleic acid. Additionally, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to conjugate the HLH peptide with resin as taught in Michigami with the gene-binding sequence of Marya and create nanostructures. One motivated to do so would have a reasonable expectation of success as the insertion of peptide sequences with nucleic acid binding properties is well-known. Thus, one would have recognized that applying the teaching of Michigami to the method of Marya, would have yielded predictable results of nucleic acid binding and improved the gene-delivery characteristics and stability of the fusion peptide as a nanostructure (See MPEP § 2143 I(A)(D)).
Conclusion
Claims 13, 14, 19 and 22 are objected to because of the dependency of the claims on a rejected claim (See MPEP § 706.01).
The following is a statement of reasons for the indication of allowable subject matter in claims
13, 14, 19, 21 and 22: Claims 13 and 14 are directed to the peptide molecule conjugate with a helicity of 0.8-0.9 and molecular length of 5-6 nm. Claim 19 is directed to a mixing ratio for the peptide molecule conjugate and nucleic acid and Claim 22 is directed to a nanostructure of the peptide molecule conjugate wherein the monolayer thickness is 5-7 nm.
The claim limitations in the above-mentioned claims are free of the prior art. Therefore claims 13, 14, 19 and 22 contain allowable subject matter.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARCHANA VARADARAJ whose telephone number is (571)272-2366. The examiner can normally be reached Monday-Friday 10:00am-5:00pm.
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/ARCHANA VARADARAJ/Examiner, Art Unit 1658
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654