DETAILED ACTION
Disposition of Claims
Claims 1-14 are pending.
Examiner’s Note
All paragraph numbers (¶) throughout this office action, unless otherwise noted, are from the US PGPub of this application US20240402182A1, Published 12/05/2024.
Applicant is encouraged to utilize the new web-based Automated Interview Request (AIR) tool for submitting interview requests; more information can be found at https://www.uspto.gov/patent/laws-and-regulations/interview-practice.
Optional Authorization to Initiate Electronic Communications
The Applicant’s representative may wish to consider supplying a written authorization in response to this Office action to correspond with the Examiner via electronic mail (e-mail). This authorization is optional on the part of the Applicant’s representative, but it should be noted that the Examiner may not initiate nor respond to communications via electronic mail unless and until Applicant’s representative authorizes such communications in writing within the official record of the patent application. A sample authorization is available at MPEP § 502.03, part II. If Applicant’s representative chooses to provide this authorization, please ensure to include a valid e-mail address along with said authorization.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 04/05/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Notably, the disclosure statement filed lists a Search Report. The listing of the references cited in a Search Report itself is not considered to be an information disclosure statement (IDS) complying with 37 CFR 1.98. 37 CFR 1.98(a)(2) requires a legible copy of: (1) each foreign patent; (2) each publication or that portion which caused it to be listed; (3) for each cited pending U.S. application, the application specification including claims, and any drawing of the application, or that portion of the application which caused it to be listed including any claims directed to that portion, unless the cited pending U.S. application is stored in the Image File Wrapper (IFW) system; and (4) all other information, or that portion which caused it to be listed. In addition, each IDS must include a list of all patents, publications, applications, or other information submitted for consideration by the Office (see 37 CFR 1.98(a)(1) and (b)), and MPEP § 609.04(a), subsection I. states, "the list ... must be submitted on a separate paper." Therefore, the references cited in the Search Report have not been considered. Applicant is advised that the date of submission of any item of information or any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the IDS, including all "statement" requirements of 37 CFR 1.97(e). See MPEP § 609.05(a).
Note: If copies of the individual references cited on the Search Report are also cited separately on the IDS (and these references have not been lined-through) they have been considered.
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 drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings. See Figure 4A, which has both amino acid and nucleotide sequences. See Fig. 5A, while the figure legend notes they are SEQ ID NOs: 77-83, it would be helpful to clarify either in the figure or the figure legend that Clone 1 = SEQ ID NO: 77, etc.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, 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
Claim 3 is objected to because of the following informalities: from the wording of the claim, claim 3 does not directly depend upon claim 1, but the use of “according to claim 1” in line 3 makes this potentially confusing. The claim does not clearly incorporate all limitations of claim 1, and should ideally be rewritten clearly in independent form. To place the claim in better form, it is suggested the claim is amended along the lines of the following: “3. An expression vector comprising a nucleotide sequence selected from the group consisting of SEQ ID NOs: 1 to 7, wherein the nucleotide sequence encodes a peptide consisting of an amino acid sequence selected from the group consisting of SEQ ID NOs: 77 to 83.” This is only one suggestion, as Applicant is free to amend the claim however they deem necessary to obviate this objection.
Appropriate correction is required.
Claim 6 is objected to because of the following informalities: to place the claim in better form in order to clearly show that the peptide comprises the sequence and also has the function of targeting the fusobacteria, it is suggested that the claim be reworded. One suggestion is: “A composition for diagnosing cancer, comprising a peptide that targets Fusobacteria and consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 77 to 83.”
Appropriate correction is required.
Claim 7 is objected to because of the following informalities: to place the claim in better form in order to clearly show that the peptide is now being further limited by the addition of a label, it is suggested that the claim be amended along the lines of the following: “The composition of claim 6, wherein the peptide is labeled with a detectable label selected from the group consisting of a color enzyme, a radioisotope, a chromophore, a luminescent substance, a fluorescent substance, super-paramagnetic particles, and ultrasuper-paramagnetic particles.”
Appropriate correction is required.
Claim 8 is objected to because of the following informalities: to place the claim in better form in order to clearly show that the cancer cell is infected with Fusobacteria, it is suggested the claim be amended along the lines of: “The composition of claim 6, wherein the peptide detects Fusobacteria infecting at least one cancer cell selected from the group consisting of colorectal cancer, melanoma, pancreatic cancer, liver cancer, stomach cancer, colon cancer, lung cancer, ovarian cancer, breast cancer, and cervical cancer.”
Appropriate correction is required.
Claim 9 is objected to because of the following informalities: to place the claim in better form in order to clearly show that the peptide comprises the sequence and also has the function of targeting the fusobacteria, it is suggested that the claim be reworded. One suggestion is: “A composition for drug delivery, comprising a peptide that targets Fusobacteria and consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 77 to 83.”
Appropriate correction is required.
Claim 11 is objected to because of the following informalities: to place the claim in better form in order to clearly show that the cancer cell is infected with Fusobacteria, it is suggested the claim be amended along the lines of: “The composition of claim 10, wherein the peptide targets the anticancer agent to Fusobacteria infecting at least one cancer cell selected from the group consisting of colorectal cancer, melanoma, pancreatic cancer, liver cancer, stomach cancer, colon cancer, lung cancer, ovarian cancer, breast cancer, and cervical cancer.”
Claim Rejections - 35 USC § 112(b); Second Paragraph
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.
Claim 1 and dependent claim 2 thereof 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 recites “a peptide targeting Fusobacteria” comprising “a peptide consisting of” an amino acid sequence selected from SEQ ID NOs: 77-83, and then recites that “the peptide” targets Fusobacteria in line 3. Because claim 1 recites two different peptides in line 1, namely an “overall peptide” which is recited first and a smaller, sequence-defined peptide recited second, it is unclear as to which “peptide” is being referenced in line 3. Further, from the wording of the claim, it is unclear if the peptide must consist of only of one of the sequences of SEQ ID NOs: 77-83, or if the peptide may instead be a larger peptide comprising said sequence. If the former interpretation is correct, one suggestion for amending the claims to overcome these issues is along the lines of the following:
“A peptide that targets Fusobacteria, the peptide consisting of an amino acid sequence selected from the group consisting of SEQ ID NOs: 77-83.”
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claim 1 is rejected on the grounds of being indefinite. Claim 2 is also rejected since it depends from claim 1, but does not remedy these deficiencies of claim 1.
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.
Claim 10 recites the limitation "the drug" in line 1. There is insufficient antecedent basis for this limitation in the claim because while claim 9 recites “A drug delivery composition”, the “drug delivery” is an intended use and the composition of claim 9 does not recite that a drug is actually in said composition, only the peptide.
For at least these reasons, the metes and bounds of claim 10 are unclear.
Claim 12 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 12 contains the trademark/trade name GLEEVEC™. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe the compound “imatinib mesylate” and, accordingly, the identification/description is indefinite.
Additionally, claim 12 uses the term “retinoic acid series”. It is unclear what is intended by this term, as it has not been defined by the specification, and the art does not clearly define this term. It is unclear if this phrase is intended to claim different generations of retinoic acid products (e.g. non-aromatic, polyaromatic, and monoaromatic retinoic acids) or if it refers to a specific type of retinoic acids.
For at least these reasons, the metes and bounds of claim 12 are unclear.
Claim 13 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 13 recites the limitation "the anticancer agent" in line 1. There is insufficient antecedent basis for this limitation in the claim.
For at least these reasons, the metes and bounds of claim 13 are unclear.
Claim 14 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 14 notes the gene drug is “small interfering RNA (siRNA) and single guide RNA (sgRNA) targeting at least one protein selected from the group consisting of” and lists a Markush group of targets. However, siRNA and sgRNA traditionally target nucleic acid, not proteins, and the Markush group comprises at least “Epstein-Barr virus” and a “BCR-ABL fusion gene” which are not proteins. It is therefore unclear if the claimed gene drug is required to target a nucleic acid encoding a listed protein, a viral nucleic acid, the BCR-ABL fusion gene or transcript, or another target associated with the item listed in the Markush group.
Accordingly, the metes and bounds of claim 14 are unclear.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
Claim 1 is drawn to a peptide targeting Fusobacteria comprising a peptide consisting of an amino acid sequence selected from the group consisting of SEQ ID NO: 77 to SEQ ID NO: 83, wherein the peptide targets Fusobacteria.
Further limitations on the peptide targeting Fusobacteria of claim 1 are wherein the peptide is displayed in a major coat protein P3 of a M13 bacteriophage (claim 2).
Claim 3 is drawn to an expression vector comprising a nucleotide sequence selected from the group consisting of SEQ ID NOs: 1 to 7, wherein the nucleotide sequence encodes a peptide consisting of an amino acid sequence selected from the group consisting of SEQ ID NOs: 77 to 83
Further limitations on the expression vector of claim 3 is wherein the expression vector is a phagemid vector (claim 4).
Claim 5 is drawn to an isolated bacterial host cell transformed with the expression vector according to claim 3.
Claim 6 is drawn to a composition for diagnosing cancer, comprising a peptide that targets Fusobacteria and consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 77 to 83.
Further limitations on the composition of claim 6 are wherein the peptide is labeled with a detectable label selected from the group consisting of a colorimetric enzyme, a radioisotope, a chromophore, a luminescent substance, a fluorescent substance, super-paramagnetic particles, and ultrasuper-paramagnetic particles (claim 7); wherein the peptide detects Fusobacteria infecting at least one cancer cell selected from the group consisting of colorectal cancer, melanoma, pancreatic cancer, liver cancer, stomach cancer, colon cancer, lung cancer, ovarian cancer, breast cancer, and cervical cancer (claim 8).
Claim 9 is drawn to a composition for drug delivery, comprising a peptide that targets Fusobacteria and consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 77 to 83
Further limitations on the composition of claim 9 are wherein the composition further comprises an anti-cancer agent that is physically or chemically bound to the peptide targeting Fusobacteria (claim 10), wherein the peptide targets the anticancer agent to Fusobacteria infecting at least one cancer cell selected from the group consisting of colorectal cancer, melanoma, pancreatic cancer, liver cancer, stomach cancer, colon cancer, lung cancer, ovarian cancer, breast cancer, and cervical cancer (claim 11), wherein the anticancer agent is selected from the group consisting of Leucovorin, Levamisole, Irinotecan, Oxaliplatin, Capecitabine, Uracil/Tegafur, Docetaxel, cis-platin, camptothecin, paclitaxel, Tamoxifen, Anasterozole, imantinib mesylate, 5-fluorouracil (5-FU), Floxuridine, Leuprolide, Flutamide, Zoledronate, Doxorubicin, Vincristine, Gemcitabine, Streptozocin, Carboplatin, Topotecan, Belotecan, Vinorelbine, hydroxyurea, nitrosourea, Valrubicin, retinoic acid series, Methotrexate, Mechlorethamine, Chlorambucil, Busulfan, Doxifluridine, Vinblastin, Mitomycin, Prednisone, Testosterone, Mitoxantron, aspirin, salicylates, ibuprofen, naproxen, fenoprofen, indomethacin, phenylbutazone, cyclophosphamide, mechlorethamine, dexamethasone, prednisolone, celecoxib, valdecoxib, nimesulide, daunorubicin, actinomycin-D, etoposide, teniposide, bisantrene, homoharringtonine, busulfan, chlorambucil, melphalan, nitrogen mustard, cortisone, and corticosteroid (claim 12); wherein the composition further comprises an anticancer agent that is physically or chemically bound to the peptide targeting Fusobacteria, and wherein the anticancer agent is a gene drug for treating cancer cells (claim 13), wherein the gene drug is selected from the group consisting of small interfering RNA (siRNA) and single guide RNA (sgRNA), wherein said siRNA or sgRNA targets at least one nucleic acid encoding at least one protein selected from the group consisting of Bcl-2 Antagonist X (Bax), B-cell lymphoma 2 (BCl-2), Focal adhesion kinase, Matrix metalloproteinase, Vascular endothelial growth factor (VEGF), Fatty acid synthase, Multiple drug resistance protein (MDR), Harvey rat sarcoma viral oncogene homolog (H-Ras), Kirsten-rat sarcoma viral oncogene homolog (K-Ras), Polo Like Kinase 1 (PLK-1), Transforming growth factor beta (TGF-β), Signal Transducer And Activator Of Transcription 3 (STAT3), Epidermal growth factor receptor (EGFR), Protein kinase C alpha (PKC-α), Epstein-Barr virus, human papillomavirus E6 (HPV E6), BCR-ABL fusion gene, and Telomerase of cancer cells (claim 14).
Claim Rejections - 35 USC § 112(a); First Paragraph
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 3-5 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for isolated expression vectors and isolated bacterial transformants, does not reasonably provide enablement for expression vectors and transformants in any broadly reasonable interpretation. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention commensurate in scope with these claims.
The claims are directed broadly to “an expression vector” and a “transformant” without limitation as to form, environment, or method of use. As such, the claim encompasses the nucleic acid vector and transformant in a wide range of contexts, including incorporation into vectors, plasmids, artificial chromosomes (e.g. bacterial or yeast artificial chromosomes (BACs or YACs)), cosmids, prokaryotic and eukaryotic cells, and organismal systems (e.g. Bacteria and Archaea, Eukaryotes (including vertebrate and invertebrate animals, plants, and fungi), and viruses).
The specification describes the claimed sequences in connection with an M13 bacteriophage/phagemid display system and generally identifies transformation techniques and certain microbial transformants. The specification does not provide guidance sufficient to enable the use of the claimed vectors and transformants across this full scope, including in complex biological systems where expression, stability, and functionality may vary depending on the host environment and delivery method.
Accordingly, undue experimentation would be required to determine how to make and use the claimed expression vectors and transformants across the full scope of the claim. It is suggested that the claims be amended to read upon “An isolated expression vector” [emphasis added] in order to overcome this rejection. With respect to “transformant”, it is suggested the claims be amended to narrow the transformant type for which the application is enabled (e.g. “A recombinant bacterial host cell comprising the phagemid vector of claim 4.” or “A recombinant isolated bacterial host cell comprising the phagemid vector of claim 4.”)
Claims 10-14 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the selection of peptides of SEQ ID NOs: 77-83, display of said peptides in a M13-based phagemid system, and detection of plated fusobacteria using the corresponding FITC-labeled peptides, does not reasonably provide enablement for the full scope of the peptide-payload compositions and cancer treatment uses recited in claims 10-14. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
The legal considerations that govern enablement determinations pertaining to undue experimentation have been set forth in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). The factors to be considered include: (1) the breadth of the claims; (2) the nature of the invention; (3) the state of the prior art; (4) the level of one of ordinary skill; (5) the level of predictability in the art; (6) the amount of direction provided by the inventor; (7) the existence of working examples; and (8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure. The factors are considered as a whole in determining whether any necessary experimentation would have been undue.
Nature of the invention and breadth of the claims. The claimed invention is directed to a therapeutic delivery composition in which a short Fusobacteria-targeting peptide is physically or chemically bound to a therapeutic payload. Claims 10-12 cover peptide compositions bound to anticancer agents, including agents with materially different structures, solubilities, mechanisms of action, cellular destinations/localizations, and release requirements. Claims 13-14 cover gene-drug compositions, including siRNA and sgRNA directed to a broad and heterogeneous group of cancer-associated targets.
The specification describes a library screen of M13 phage-displayed peptides which bind to Fusobacteria, namely 9 specific types of Fusobacteria (¶[0061]), wherein peptides consisting of SEQ ID NOs:77-83 were identified as binding to the panned bacteria (¶[0063-0085]). The corresponding peptides were then bound to fluorescein isothiocyanate (FITC) and were co-plated with different types of Fusobacteria (¶[0084-0089]). These teachings do not reasonably provide enablement for the full scope of the peptide-payload compositions and cancer treatment used recited in the claims, as claims 10-14 are not limited to the disclosed embodiments. The claims also encompass chemical anticancer agents and gene drugs physically or chemically bound to the peptide, while also requiring treatment of cancer cells infected with Fusobacteria. The claimed scope therefore extends beyond the embodiments of peptide selection, phage binding, and FITC-detection described in the specification.
State of the prior art and predictability of the art. At the time the application was filed, persons of ordinary skill knew that targeted phage and peptide-conjugated drug delivery systems required deliberate selection of the targeting moiety, payload, carrier construction, conjugation chemistry, and mechanism of release of said drug to said target. Such systems were not predictable merely because a targeting ligand could be labeled with a fluorophore.
For example, Bar et. al. (Bar H, et. al. BMC Biotechnol. 2008 Apr 3;8:37.) describes drug carrying filamentous phage in which a target-specific ligand was displayed on the phage and either hygromycin or doxorubicin was chemically conjugated to the phage. Bar used different attachment approaches for the different payloads, wherein hygromycin was coupled through an amide bond, while doxorubicin was attached through engineered cathepsin-B-cleavable sites. Bar further reported that direct covalent linkage of doxorubicin to the phage was inefficient for growth inhibition, whereas the phage carrying doxorubicin through the cathepsin-B-releasable linkage was more efficient. Bar explained that the results varied with the particular drug and targeting moiety, and identified drug release, drug loading, target internalization, and target abundance as critical design variables.
Likewise, Yacoby et. al. (Yacoby I, et. al. Antimicrob Agents Chemother. 2007 Jun;51(6):2156-63. Epub 2007 Apr 2.) report that a prior phage drug system had limited drug loading capacity because of the hydrophobicity of the payload. Yacoby used an aminoglycoside-based branched linker to improve solubility and loading of chloramphenicol (CAM), producing a different phage-drug conjugation architecture from the earlier direct conjugation approach. Yacoby explained that a useful targeted drug carrier requires binding specificity, sufficient payload, and a programmed release mechanism. This prior art work demonstrates that the behavior of a drug carrying phage or peptide system depended upon the physiochemical properties of the payload and how said payload was attached to the peptides.
A recent review article by Fu et. al. (Fu C, et. al. Acta Pharm Sin B. 2023 Feb;13(2):498-516. Epub 2022 Aug 3.) summarizes the pros and cons of peptide-drug conjugates (PDCs) and state that while they have enhanced cellular permeability and improved drug selectivity, there are significant issues in the development of PDCs due to poor stability, low bioactivity, long research and development time, and slow clinical development process as therapeutic agents. Fu notes the choice of peptide affects the efficiency of drug endocytosis in PDCs, and once the target has been selected, the selection of a suitable peptide for the PDC is also important and has a significant impact on efficacy, pharmacokinetic/pharmacodynamic profile, and therapeutic indices. Fu teaches the ideal peptide for PDCs should have a strong target binding affinity, high stability, low immunogenicity, efficient internalization, and a long plasma half-life. Fu summarizes that while the PDC technology has its advantages, that there are still many “hard bones” to overcome with the technology.
The prior art further indicates that delivery of siRNA and CRISPR-based sgRNAs required separate consideration of RNA stability, cellular uptake, endosomal escape, and intracellular activity. Tai et. al. (Tai W, et. al. Adv Drug Deliv Rev. 2017 Feb;110-111:157-168. Epub 2016 Aug 13.) review peptide-assisted siRNA delivery systems and describe the use of distinct functional components for cell targeting, nucleic acid condensation, cellular entry, and endosomal escape. Tai notes a large number of peptides with specific affinity to disease-associated biomolecules have been identified through biopanning, site-specific mutagenesis of natural peptide sequences, and computer-aided design, but highlights that localization to the siRNA to the correct intracellular compartment upon delivery remains an issue, as endosomes trap the siRNA payload and prevent its release. Hou et. al. (Hou KK, et. al. Biotechnol Adv. 2015 Nov 1;33(6 Pt 1):931-40. Epub 2015 May 27.) also highlights this issue with endosomal entrapment, showing that peptide-mediated siRNA transfection was limited by endosomal entrapment and that additional strategies, including lipid conjugation, fusogenic peptides, activation mechanisms, and endosomal release approaches were still being developed to overcome this known issue.
For sgRNA based systems, Finn et. al. (Finn JD, et. al. Cell Rep. 2018 Feb 27;22(9):2227-2235.) developed a defined lipid nanoparticle (LNP) formulation for co-delivery of CRISPR/Cas9 components. Finn reports that the chemical modification pattern of the sgRNA was important for high in vivo activity and that the delivery system needed to transport the Cas9 component together with one or more guide RNAs. Finn teaches that the ideal delivery system for CRISPR/Cas9 requires a number of key attributes that include (1) a transient, non-integrating Cas9 expression construct to limit potential off-target events, immune responses, and integration events into the genome; (2) efficient delivery with the capacity to transport the large Cas9 enzyme (or its encoding mRNA) as well as one or more sgRNAs; and (3) the option to redose should the effect wane over time or require repeat dosing to reach a therapeutically relevant level of editing; and (4) scalability of the formulation to enable large-scale manufacturing to address both orphan and common diseases. Finn highlights that sgRNA cannot simply be delivered to a system on its own, and requires co-delivery with the Cas9 protein or nucleic acid encoding said protein.
The art, taken as a whole, was not sufficiently predictable to support extrapolation from FITC-labeled peptide bound to plated bacteria to every peptide-anticancer agent composition or peptide-gene drug composition recited in claims 10-14. As the art showed, attachment of a payload was not merely a labeling exercise. The particular payload, mode of attachment, type of peptide, mechanism of release in/near the target cell, and intracellular delivery requirements could change whether or not a composition retained Fusobacteria binding and achieved the claimed therapeutic result. Accordingly, the results obtained using would not have reasonably established that the broader claimed scope could be practiced without further experimentation.
Level of skill in the art. One skilled in the art would have been familiar with peptide synthesis, FITC-labeling, phage display, ELISA assays, standard chemical-conjugation methods, cell culture, siRNA design, and CRISPR/Cas9 (sgRNA) systems. However, the existence of known methods for preparing and testing candidate embodiments does not establish that one skilled in the art would have known, without further experimentation, which additional linking agents, anti-cancer agents, or gene drugs (namely siRNA or sgRNA) would satisfy the claimed therapeutic activity.
Working examples. The specification provides working examples directed to phage-display selection of peptide sequences, phagemid cloning, ELISA testing of peptide-displaying phage, and detection of plated fusobacteria using peptides conjugated to FITC (Examples 2-3; Figs. 4-5).
The specification does not provide working examples directed to a peptide consisting of SEQ ID NO: 77-83 bound to any anticancer agent recited in claim 12. It does not provide data showing retained fusobacteria binding after attachment of a chemical anticancer agent, payload loading, serum or formulation stability testing in vivo, targeting/release of the anticancer agent to the appropriate cell type, or exerted treatment effect of the payload being delivered to the cancer cells. The specification also does not provide any examples of siRNA or sgRNA bound to any of the peptides, or any other gene drugs bound to said peptides. No siRNA sequence, sgRNA sequence, target nucleotide sequence, Cas component (e.g. nucleic acid or protein), evidence of target cell nucleic acid modification (e.g. gene silencing), peptide-RNA linkage, specific pharmaceutical formulations, any intracellular delivery localization studies, or any other anti-cancer therapeutic result is described. The disclosed examples therefore do not establish enablement across the full scope of claims 10-14.
Guidance in the specification. The specification provides general guidance that anticancer agents may be bound to the peptides “in the same manner as FITC.”(Example 3) The specification also includes a schematic discussion in which a fusobacteria-targeting peptide is displayed on M13 P3 and a chemical anticancer agent is packaged with dextran and linked to P8 and P9 through a cross-linker (Figs. 6-8). However, the specification does not provide sufficient guidance regarding the full scope of claims 10-14, as these claims do not require M13 bacteriophage, P3 display, P8 or P9 attachment, dextran packaging, a specific cross-linker or other linking agent, or any defined mechanism to release the payload from the targeting peptide. The specification does not explain whether an anticancer agent is to be directly attached to the short peptide, attached through a cleavable linker, attached through a carrier, noncovalently complexed, or displayed on a phage particle. Additionally, the specification fails to provide guidance for determining which of the chemically diverse anticancer agents of claim 12 may be attached without disrupting the fusobacteria-binding property of the disclosed peptide, which linker conditions yield an active released anticancer drug, or which formulations can deliver the payload into the claimed cancer cells. The same gap is even greater for claims 13-14, as a mere listing of siRNA and sgRNA as potential gene drugs and a list of potential biological targets does not identify a general quality or provide a structure-function correlation that predicts which RNA sequences, guide designs, RNA modifications, peptide-RNA conjugates, or delivery conditions will achieve the claimed therapeutic result.
Quantity of experimentation necessary. To practice the full scope of claims 10-12, one skilled in the art would need to select a payload from the broad group of anticancer agents, determine an appropriate chemistry compatible with the payload and the peptide, prepare the resulting composition, and test whether the composition retains Fusobacteria binding. To practice the full scope of claims 13-14, one skilled in the art would need to select one or more siRNA or sgRNA sequences for the claimed targets, determine the relevant target sequence and guide site, select a means for protecting and delivering the RNA, and establish an attachment or complexation strategy that permits intracellular release and biological activity. For the sgRNA embodiments, the skilled artisan would need to select a compatible CRISPR nuclease system. For all claims, further experimentation would be necessary to determine payload loading, stability, release, uptake, and whether the composition delivers a therapeutic amount of the payload to the target cell.
Such experimentation would not merely involve the routine application of known methods to embodiments reasonably expected to work. The relevant inquiries are not whether one skilled in the art could synthesize these peptide-anticancer drug/peptide-gene drug constructs, but whether the specification provides sufficient guidance to identify and practice the embodiments falling within the full scope of the claims without undue experimentation. In the instant application and claims, one skilled in the art would need to prepare and test additional embodiments to determine whether they satisfy the claimed function of fusobacteria targeting and provide the claimed treatment of cancer cells.
Amgen. The Supreme Court has explained that a specification need not describe with particularity how to make and use every embodiment within a claimed class. However, the disclosure must enable one skilled in the art to make and use the full scope of the claimed invention. A reasonable amount of experimentation may be permissible depending on the nature of the invention and the underlying art. Amgen Inc. v. Sanofi, 598 U.S. 594, 610-13 (2023).
In the instantly claimed invention, the specification describes peptide-FITC composition embodiments, but the claims also encompass the peptide having any other gene drug or anticancer payload attached through any means and having said resulting peptide-drug conjugate be therapeutically effective in the treatment of cancer. The specification does not identify a general quality of the peptide-payload compositions, or provide sufficient guidance, that would allow one skilled in the art to practice that materially broader scope without undue experimentation.
Conclusion. For the reasons discussed above, the specification does not enable one skilled in the art to make and use the full scope of the invention recited in claims without undue experimentation.
Claims 13-14 are rejected under 35 U.S.C. 112(a), or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The written description requirement is separate and distinct from the enablement requirement. To satisfy the written description requirement, the specification must reasonably convey to one skilled in the relevant art that the inventor had possession of the claimed invention as of the filing date. Possession may be shown by a description of the complete structure of the claimed invention, a representative number of species falling within the scope of a claimed genus, or relevant identifying characteristics sufficient to show that the inventor had possession of the claimed subject matter.
Claims 13-14 recite wherein the peptide composition for drug delivery further comprises an anticancer agent that is physically or chemically bound to the peptide targeting Fusobacteria, and wherein the anticancer agent is a gene drug for treating cancer cells, and states the gene drug may be small interfering RNA (siRNA) or single guide RNA (sgRNA) and provides examples of what said RNA may target.
The specification describes selection of peptides of SEQ ID NOs: 77-83 using an M13 phage display system, binding assays using the peptide-displaying phage, and FITC-labeled peptides tested for binding to fusobacteria (¶[0015-0017][0040-0042][0057-0069]). The specification also generally identifies a gene drug as an anticancer agent embodiment and identifies siRNA and sgRNA directed to the recited target group (¶[0028-0029]).
However, the scope of claims 13-14 is not limited to the embodiments described in the specification. The claims broadly encompass any peptide-gene drug composition, and the specification does not describe a representative number of examples of any of these. No embodiment identifies an siRNA sequence, an sgRNA spacer sequence, a target nucleic acid region, an RNA modification pattern, a peptide-RNA linkage or resulting complex, a carrier formulation of said resulting complex, or a compatible complete system for sgRNA (e.g. inclusion of a Cas endonuclease) embodiment. It is unclear how the peptide-RNA would be stabilized in vivo (e.g. inclusion in a liposome or LNP carrier). The specification also provides no data showing that a peptide of SEQ ID NOs: 77-83 remains fusobacteria targeting after association with any gene drug, delivers said gene drug to cancer cells infected with fusobacteria, or produces gene silencing, gene editing, or the claimed treatment result.
The claims are not limited to the disclosed peptide-FITC embodiments or to the M13 phage display system. Instead, claim 13 encompasses gene drugs broadly, and claim 14 encompasses siRNA and sgRNA species directed to each member of the listed target group. The specification does not identify structural features common to peptide gene-drug compositions that would allow one of skill in the art to recognize which additional compositions possess the recited targeting and therapeutic properties.
The disclosure of gene drugs, siRNA, sgRNA, and potential targets as categories does not reasonably convey possession of the broad functional genus recited in claims 13-14. One skilled in the art would be required to select additional RNA species, attachment or complexation arrangements, and delivery formats not described in the specification and then determine whether those embodiments satisfy the claimed limitations.
Accordingly, the disclosure does not reasonably convey to one skilled in the art that the inventor had possession of the full scope of the subject matter recited in claims 13-14 at the time the application was filed.
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.
Claims 1-6 and 9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Creative Biolabs (Creative Biolabs. “Premade Phage Display Peptide Libraries.” 07/27/2021. https://www.creative-biolabs.com/premade-phage-display-peptide-libraries.html. Accessed via WayBackMachine.com; hereafter “Creative Biolabs”) as evidenced by Creative Biolabs (Creative Biolabs. “Phage Display TriCo-C9 Cyclic 9-mer Peptide Library Licensing/Screening Service.” https://www.creative-biolabs.com/trico-c9-peptide-library-licensing-screening-service.html. Accessed 06/24/2026; hereafter “Creative Biolabs-1”).
The Prior Art
Creative Biolabs teaches a TriCo-C9 cyclic 9-mer peptide library and an associated library screening service. The peptides are displayed in a phagemid display system, namely an M13 pIII fusion display, and are expressed from a vector (pCDisplay-3M) in E. coli (p. 3 “TriCo-C9™ Phage Display Peptide Library; See also Creative Biolabs-1 “Basic Library Information”, p. 2;; instant claims 2, 5). The phagemid library vector map is present on p. 3 of Creative Biolabs-1, and shows the DNA vector which expresses the 9-mer peptide fragments (instant claims 3-4). This TriCo-C9 Phage Display Peptide Library has a capacity of 8.6x10^10 members (p. 3 “TriCo-C9™ Phage Display Peptide Library”). As evidenced by ¶[0070] of the specification, these identifying characteristics listed by the Creative Biolabs TriCo-C9 Peptide Library appear to be the same as the phage display library system of the instant invention. Said library therefore inherently comprises the peptides as identified as SEQ ID NOs: 77-83, and the nucleotide sequences of SEQ ID NO s: 1-7.
The same pre-existing displayed peptide clones necessarily possessed the same ability to bind Fusobacteria when present in Creative Biolabs TriCo-C9 library. The fact that Creative Biolabs did not expressly identify Fusobacteria as a target does not avoid anticipation because a newly recognized property of an otherwise identical prior art composition is inherent (MPEP §2112.I-II.) The instant specification is cited only as extrinsic evidence establishing that the relevant peptide species and their Fusobacteria-binding property were necessarily present in the TriCo-C9 library of Creative Biolabs. The instant specification explains that the library was contacted with Fusobacteria, unbound phage were removed, bound phage were eluted and amplified through repeated panning rounds, and individual enriched clones were then sequenced (¶[0070]). Additionally, claim 1 does not require the peptide to be isolated, cleaved from the phage-display construct, chemically synthesized, linear, or otherwise removed from the M13 display system. Accordingly, the TriCo-C9 phage display library of Creative Biolabs as evidenced by Creative Biolabs-1 inherently comprises nucleic acid of SEQ ID NOs: 1-7 which encodes/expresses the peptides of SEQ ID NOs: 77-83 and inherently possesses the recited Fusobacteria-targeting property, and anticipates instant claims 1 and 3.
Furthermore, claim 6 recites a composition for diagnosing cancer, including a peptide consisting of SEQ ID NOs: 77-83. The phrase “for diagnosing cancer” does not impose a further structural limitation on the composition and is an intended use. Therefore, Creative Biolabs also anticipates the limitations of instant claim 6.
Additionally, claim 9 recites a composition for drug delivery, including a peptide consisting of SEQ ID NOs: 77-83. The phrase “for drug delivery” or a “drug delivery composition” does not impose a further structural limitation on the composition and is an intended use. Therefore, Creative Biolabs also anticipates the limitations of instant claim 9.
For at least these reasons, Creative Biolabs, as evidenced by Creative Biolabs-1, expressly or inherently teaches every limitation of instant claims 1-6 and 9, and anticipates the invention encompassed by said claims.
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.
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.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Creative Biolabs as evidenced by Creative Biolabs-1 as applied to claims 1-6 and 9 above, and further in view of Eckert et. al. (US20100184681A1; Pub. 07/22/2010; hereafter “Eckert”.
The Prior Art
The teachings of Creative Biolabs has been set forth supra. While Creative Biolabs teaches that the peptides may be conjugated to a his or myc tag, Creative Biolabs fails to teach a fluorescent or colorimetric tag attached to the peptide. However, such attachment would be obvious given the teachings of Eckert.
Eckert teaches novel antimicrobial peptides and formulations thereof. The peptides and/or formulations are effective to kill or to inhibit the growth and/or proliferation of various bacteria, yeast, and fungi (entire document; see abstract.) Eckert teaches peptides which are effective against Fusobacterium nucleatum (¶[0010][0012][0033][0063][0078]; reference claims 6, 10, 52; Tables 2-3, 5, 8.) Eckert teaches that the peptides can be “STAMPs”, which stands for specifically targeted anti-microbial peptides (¶[0057]). Eckert provides peptides that are effective targets of F. nucleatum (Table 5), and teaches that said peptides may be attached to fluorescent dyes (such as fluorescein), colorimetric labels, magnetic or paramagnetic nanoparticles, and enzymes (¶[0095]).
It would have been obvious to label the Fusobacteria-targeting peptide of Creative Biolabs with fluorescein or another detectable label in view of Eckert, in order to detect the presence or location of Fusobacteria. Eckert teaches attaching detectable labels to microorganism-targeting peptide constructs, including peptides active against Fusobacterium, for that purpose. Therefore, the limitations of instant claim 7 would be obvious to a skilled artisan.
It would have been obvious to one of ordinary skill in the art to modify the compositions taught by Creative Biolabs in order to tag the peptide with a detectable label, thereby allowing it to visually be detected in target cells. One would have been motivated to do so, given the suggestion by Eckert that Fusobacterium-targeting peptides could be labeled with detectable reagents, such as fluorescein. There would have been a reasonable expectation of success, given the knowledge that colorimetric, luminescent, and fluorescent markers were added to Fusobacterium-targeting peptides, as taught by Eckert. Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Creative Biolabs as evidenced by Creative Biolabs-1 as applied to claims 1-6 and 9 above, and further in view of Han et. al. US20140206011A1, Pub. 07/24/2014; hereafter “Han”.)
The Prior Art
The teachings of Creative Biolabs has been set forth supra. While Creative Biolabs teaches peptides that inherently bind to Fusobacterium, Creative Biolabs fails to teach the use of said peptides for the detection of cancer cells infected by Fusobacterium. However, such detection use would be obvious given the teachings of Han.
Han teaches measuring F. nucleatum in a biological sample can indicate increased colorectal cancer (CRC) risk and can differentiate between precancerous and cancer states (entire document; see abstract; reference claim 1). Han teaches that a targeting small molecule, polypeptide, or antibody can be used to bind to FadA on the bacteria (¶[0093-0108]) and can be conjugated to other items (¶[0097]) and can be linked to detectable moieties (¶[0105]), such as labeled by fluorescent dyes, chemiluminescent agents, magnetic labels, or radionucleotides (¶[0037]).
It would have been obvious to detect the Fusobacteria-targeting peptide of Creative Biolabs in view of Han, which teaches the detection of Fusobacteria correlates to the presence/risk of CRC. Han teaches attaching detectable labels to polypeptide constructs which can bind to the Fusobacteria, including peptides active against Fusobacterium. Therefore, the limitations of instant claim 8 would be obvious to a skilled artisan.
It would have been obvious to one of ordinary skill in the art to use the compositions taught by Creative Biolabs in order to use said peptide to aid in the detection of Fusobacterium, thereby aiding in the therapeutic diagnosis of CRC risk. One would have been motivated to do so, given the suggestion by Han that Fusobacterium-targeting polypeptides could be labeled with detectable reagents. There would have been a reasonable expectation of success, given the knowledge that the association of Fusobacterium and CRC was known, and that polypeptides which targeted Fusobacterium were known and could be labeled with detectable tags, as taught by Han. Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Claims 10 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Creative Biolabs as evidenced by Creative Biolabs-1 as applied to claims 1-6 and 9 above, and further in view of Beliveau et. al. (US20200392184A1; Pub. 12/17/2020; hereafter “Beliveau”) and Dong et. al. (Dong X, et. al. Sci Adv. 2020 May 15;6(20):eaba1590.; hereafter “Dong”.)
The Prior Art
The teachings of Creative Biolabs has been set forth supra. While Creative Biolabs teaches peptides that inherently bind to Fusobacterium, Creative Biolabs fails to teach the use of said peptides for the treatment of cancer cells infected by Fusobacterium by attaching an anti-cancer agent to said peptide. However, such peptide-anticancer combination would be obvious given the teachings of Beliveau.
Beliveau teaches a therapeutic conjugate in which a therapeutic agent is connected to the peptide at an N-terminus, free amine, a thiol group, or carboxyl group, optionally through a linker (entire document; see abstract; ¶[0039][0128][0122-0142]). Beliveau teaches that doxorubicin is one of the therapeutic agents that can be bound to the peptide (¶[0180][0273][0279]).
Dong teaches Fusobacterium nucleatum (Fn) contributes to CRC tumorigenesis, and teaches that an M13-binding phage that specifically binds to Fn was screened by phage display technology. Then silver nanoparticles were assembled onto the surface capsid protein of the phage (M13@Ag) to achieve specific clearance of Fn and remodel the tumor microenvironment (entire document; see abstract.) Dong teaches that these phage combined with immune checkpoint inhibitors (anti-PD1) or chemotherapeutics (FOLFIRI) significantly prolonged overall survival in the mouse model (abstract; Fig. 6).
It would have been obvious to chemically attach doxorubicin to the Fusobacteria-targeting peptide of Creative Biolabs, as taught by Beliveau, in order to provide a targeted therapeutic composition. One would have been motivated to do so because Dong taught that an Fn-binding M13 phage platform could be used to selectively target and deliver anticancer agents to Fn in a CRC setting and exert a therapeutic effect. Therefore, the limitations of instant claims 10 and 12 would be obvious to a skilled artisan.
It would have been obvious to one of ordinary skill in the art to use the compositions taught by Creative Biolabs in order to use said peptide to aid in the treatment of Fusobacterium, such as using a targeting platform, such as a peptide, to deliver therapeutic agents to the bacterium. One would have been motivated to do so, given the suggestion by Beliveau that polypeptides could be labeled with anticancer therapeutics such as doxorubicin. There would have been a reasonable expectation of success, given the knowledge that the association of Fusobacterium and CRC was known, and that M13 platforms which targeted Fusobacterium were known and could be associated with anticancer agents that treated the CRC model, as taught by Dong. Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure and is listed below.
Choudhury A, et. al. Microb Biotechnol. 2025 Dec;18(12):e70241. Post-filing art related to the technology of targeting peptides to Fusobacterium.
Liu Z, et. al. ACS Infect Dis. 2024 Aug 9;10(8):3042-3051. Epub 2024 Jun 26. Post-filing art related to the technology of targeting peptides to Fusobacterium.
Ganesan K, et. al. Cancers (Basel). 2019 Oct 18;11(10):1592. Teaches that Fusobacterium are known to be associated with colorectal cancer and teaches targeting Fusobacterium for treatment of colorectal cancer. Not utilized as rejection would be redundant to those set forth supra.
Slade DJ. Trends Cancer. 2021 Mar;7(3):185-187. Epub 2020 Dec 9. Abstract only. Teaches potential therapy for colorectal cancer by targeting Fusobacterium. Not utilized as rejection would be redundant to those set forth supra.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RACHEL B GILL whose telephone number is (571)272-3129. The examiner can normally be reached on M to F 8:00 AM to 5:00 PM Eastern.
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/RACHEL B GILL/
Primary Examiner, Art Unit 1671
Prosecution Insights