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 .
Status of Claims
The claim listing filed June 24, 2024 is pending. Claim 18 is cancelled. Claims 1-17 are pending. Claims 1-17 are rejected.
Priority
Applicant’s claim for the benefit of a provisional application filed under 35 U.S.C. 111 is acknowledged. Claims 1-17 have eligible subject matter and are subjected to the priority date of 08/23/2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on December 20, 2023 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is considered by the examiner.
Claim Rejections - 35 USC § 112
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 10-17 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 treating breast cancer, colorectal cancer, prostate cancer, gastric cancer, ovarian cancer, squamous cell carcinoma, and non-small lung cancer as the therapeutic targets of the MIEN1-derived peptides with the administrations of amino acid peptides consisting of SEQ ID NO:7 and consisting of SEQ ID NO: 7, does not reasonably provide enablement for “treating all cancer” or inhibiting the migration of all cancers. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Using the word “cancer” translates to any type of uncontrollable cell proliferation. This means using the broadest reasonable interpretation, the method of using the therapeutic peptides would apply any type of uncontrollable cell proliferation. The inventors aim to treat various cancers using MIEN-1 derived peptides of 6 to 7 amino acids. In the specifications, the word treating is defined as:
"Treating" means that following a period of administering the therapeutic peptide or composition comprising a therapeutic peptide, a beneficial therapeutic and/or prophylactic result is achieved, which can include a decrease in the severity of symptoms or delay in or inhibition of the onset of symptoms, increased longevity and/or more rapid or more complete resolution of the disease or condition, or other improved clinical outcome as measured according to the site that is being observed or the parameters measured for a particular disease or disorder.
In the results section, the inventors show that the MIEN1-derived peptides RP-7 and LA3IK inhibits the phosphorylation of focal adhesion kinase (FAK), inhibiting cellular adhesion and actin dynamics. However, not every cancer’s progression correlates to FAK. Furuyama et al concluded that FAK expression is not directly related to clinicopathological factors except tumor size in pancreatic carcinoma, and therefore may not be a prognostic marker for pancreatic cancer patients.
(Furuyama, K., Doi, R., Mori, T., Toyoda, E., Ito, D., Kami, K., Koizumi, M., Kida, A., Kawaguchi, Y., & Fujimoto, K. (2006). Clinical significance of focal adhesion kinase in resectable pancreatic cancer. World journal of surgery, 30(2), 219–226. https://doi.org/10.1007/s00268-005-0165-z)
The inventors also state that LA3IK and RP-7 reverse epithelial to mesenchymal transition (EMT) markers such as SLUG, SNAIL, MMP 9 , N-Cadherin and Zeb-1in prostate cancer cells. As Vaaikar et al states:
“EMT confers properties that result in dissociation of tumour cells from the primary tumour mass, invasion through the extracellular matrix, intravasation into blood vessels and colonisation of distant organs, and re-activation of epithelial properties at the secondary site via the MET cause metastases, the primary cause of death in cancer patients.”
(Vasaikar, S.V., Deshmukh, A.P., den Hollander, P. et al. EMTome: a resource for pan-cancer analysis of epithelial-mesenchymal transition genes and signatures. Br J Cancer 124, 259–269 (2021). https://doi.org/10.1038/s41416-020-01178-9)
Mak et al., performed a pan-cancer analysis, identifying 77 gene signatures from 11 cancer types associated with EMT using clinical patient samples from The Cancer Genome Atlas.
(Mak, M. P., Tong, P., Diao, L., Cardnell, R. J., Gibbons, D. L., William, W. N., Skoulidis, F., Parra, E. R., Rodriguez-Canales, J., Wistuba, I. I., Heymach, J. V., Weinstein, J. N., Coombes, K. R., Wang, J., & Byers, L. A. (2016). A Patient-Derived, Pan-Cancer EMT Signature Identifies Global Molecular Alterations and Immune Target Enrichment Following Epithelial-to-Mesenchymal Transition. Clinical cancer research: an official journal of the American Association for Cancer Research, 22(3), 609–620. https://doi.org/10.1158/1078-0432.CCR-15-0876)
The authors selected candidate genes from the mRNAs that best correlated with four established EMT markers: E-cadherin (CDH1), vimentin (VIM), fibronectin (FN1), and N-cadherin (CDH2). However, out of the 11 cancer types they tested, they were unable to use kidney renal clear cell carcinoma (KIRC) or rectal adenocarcinoma (READ) tumors to develop the pan-cancer EMT signature because they found cancers with mesenchymal (KIRC) or epithelial (READ) tumors have a low dynamic range of EMT.
The inventors performed cell studies with the MDA-MB-231 cell line which is representative of the Triple Negative Breast Cancer, and the DU145 cell line, which is representative of prostate adenocarcinoma, but there is a lack of predictability for treating any type of cancer with one therapeutic, such as the composition of SEQ ID NO:4 and SEQ ID NO:7.
This is supported by the prior art because the MIEN1-derived peptides inhibit the phosphorylation of FAK, but FAK expression is not directly related to clinicopathological factors except tumor size in pancreatic carcinoma. Also, the MIEN1-derived peptides reverse EMT markers, but KIRC and READ have a low dynamic range of EMT markers. One of ordinary skill in the art can determine with the prior art that MIEN1-derived therapeutic peptides are not credibly enabled to treat every type of cancer.
However, the prior art does support treating breast cancer, colorectal cancer, prostate cancer, gastric cancer, ovarian cancer, squamous cell carcinoma, and non-small lung cancer. This is because the study by Mak et al, found EMT markers in all of the above cancer types. A review by Golubovskaya also found FAK to be elevated in all of the above cancers except for gastric cancer.
(Golubovskaya V. M. (2010). Focal adhesion kinase as a cancer therapy target. Anti-cancer agents in medicinal chemistry, 10(10), 735–741. https://doi.org/10.2174/187152010794728648)
Therefore, there exists a predictability that these cancers may be treated by SEQ ID NO:4 and SEQ ID NO:7.
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 1-17 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 uses the language “comprising one or more therapeutic peptides,” and goes on to claim a composition that has SEQ ID NO:4 and SEQ ID NO:7. This language is indefinite because the composition inherently has two peptides with the use of the word “and.” Therefore, this claim in accordance with the broadest reasonable interpretation, has been interpreted as a composition comprising of both individual peptides.
Claims 2 and 3 recites the limitation "the therapeutic peptide or peptides" in line 1 of claim 2 and line 2 of claim 3. There is insufficient antecedent basis for this limitation in the claim because it is unclear if “the therapeutic peptide’ is referring to the first or the second therapeutic peptide in claim 1 or if it is referring to one of the peptides encompassed by the phrase “more therapeutic peptides”.
Claim 3 recites the limitation ‘the therapeutic peptide or peptides further comprise a heterologous peptide.” For the purposes of compact prosecution and using the broadest reasonable interpretation, this limitation is interpreted as any composition comprising of the first or/and second therapeutic peptide with any heterologous portion
Claim 9 recites the limitation "the peptide" in line 2. There is insufficient antecedent basis for this limitation in the claim because it is unclear if ‘the peptide’ is referring to the first, second or any other therapeutic peptide in claim 1.
Claim 12 recites “the therapeutic peptide.” Claim 15 has the same issue. There is insufficient antecedent basis for this limitation because it is unclear if ‘the therapeutic peptide’ is referring to the six amino acid peptide, the seven amino acid peptides, or some other peptide in the composition.
Claims 12 and 13 recites the limitation "at least a second anti-cancer agent" in line 2 of claim 12 and line 1 of claim 13. The claims are indefinite because it is not specified what the first anti-cancer agent is. It is indeterminate whether the applicant is referring one of the therapeutic peptides or the composition of both as the first or second anti-cancer agent, and if so which one. It could also be that the applicant is referring to an anti-cancer agent listed in the specification. If it is the latter, the applicant may incorporate the possible anti-cancer agent compounds from the specifications.
"Reading a claim in light of the specification, to thereby interpret limitations explicitly recited in the claim, is a quite different thing from ‘reading limitations of the specification into a claim,’ to thereby narrow the scope of the claim by implicitly adding disclosed limitations which have no express basis in the claim (See MPEP §2111)." See also in re Morris, 127 F.3d 1048, 1054-55, 44 USPQ2d 1023, 1027-28 (Fed. Cir. 1997)
Therefore, the possible anti-cancer agents listed in the specifications cannot be used to implicitly limit the claim.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 16 recites the broad recitation “having”, and the claim also recites “six amino acid peptides,” “a seven amino acid peptide, a six amino acid peptide having an amino acid sequence of LAIA VK (SEQ ID NO:4) and a seven amino acid peptide having an amino acid sequence of RPPCVIL” which is the narrower statement of the range/limitation. In the specifications, the applicant gives the word ‘having’ a non-limiting definition:
"having" (and any form of having, such as "have" and "has"), "including" (and any form of including, such as "includes" and "include") or "containing" (and any form of containing, such as "contains" and "contain") are inclusive or open- ended and do not exclude additional, unrecited elements or method steps.”
The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. It is unclear whether the applicant what is limiting; the peptide limited to six and/or seven amino acids or does it just have to have the six residues of SEQ ID NO:4 and/or the seven residues of SEQ ID NO:7 in the composition. The applicant may remedy this by using a limiting term such as ‘consisting of’ of describe the number of amino acids in each peptide.
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.
Claims 1, 2, 7, and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Faris et al. (US20020055478A1; published 2002) and Zauderer et al. (US20070081942A1: published 2007).
Faris et al. provide polypeptide fragments that bind to 103P3E8 proteins as a diagnostic and/or therapeutic target for cancers that over-express the gene 103P3E8. Among the tissues that express 103P3E8 when malignant are prostate bladder, kidney, colon, lung, breast, rectum, and stomach (Table 1). The patent publication presents a 10-mer sequence (SEQ NO: 274) that terminally comprising the sequence LAIA VK (Table VI and X). Faris et al. does not teach the second therapeutic peptide in the composition.
Zauderer et al. is about a formulation and use of the C35 gene and polypeptides in immunogenic compositions or vaccines, to induce antibody and cell-mediated immunity against tumor cells that differentially express the C35 gene. This may include tumor of the bladder, lung and breast [0227]. The peptides are derived from the sequence translated by the C35. The second therapeutic peptide claimed by the applicant is comprised in the peptides that have a start position of 106 on the C35 peptide for the nonamers and 107 for the octamers, such as SEQ NO: 115 (see HLA peptide motif search results in specifications).
Therefore, it would have been obvious to a person of ordinary skill before the effective filing date of the claimed invention to combine the therapeutic peptide from US20020055478 comprising of SEQ ID NO:4 and the therapeutic peptide from US20070081942 comprising of SEQ ID NO:7 to make the composition of claim 1 There would have been a reasonable expectation of success because they both individually treat lung and breast cancer. It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose (See MPEP §2144.06)
Regarding claim 2, both Faris and Zauderer teach amino and carboxy modifications. Faris et al., states that covalent modifications of the 103P3E8 peptides such as those on the N- or C- terminal residues are within the scope of the invention [See 0168]. Zauderer et al. also states that the modifications of C35 polypeptides can occur on “the peptide backbone, the amino acid side-chains and the amino or carboxyl termini” [See 0043]. Thus, it would have been obvious before the effective filing date of the claimed invention to modify and the amino and carboxy terminals.
Regarding claim 7, Faris et al. teach therapeutic compositions used in the practice of the foregoing methods can be formulated into pharmaceutical compositions comprising a carrier suitable for the desired delivery method [See 0267]. It would have been obvious before the effective filing date of the claimed invention to add a delivery vehicle to the composition with a reasonable expectation of successfully delivery as desired as taught by Faris et al.
Regarding claim 8, secondary reference Zauderer et al. teaches liposome delivery [See 0337]. It teaches that the lipid content can be adjusted to optimized secreted polypeptide for therapeutic use. It would obvious to one ordinary skill of the art before the filing date using this reference to use a liposome for optimal delivery.
Claims 3-5 are rejected under 35 U.S.C. 103 as being unpatentable over Faris et al. and Zauderer et al. as applied to claim 1 above, and in further view of Deng et al.
(Deng, T., Ge, H., He, H., Liu, Y., Zhai, C., Feng, L., & Yi, L. (2017). The heterologous expression strategies of antimicrobial peptides in microbial systems. Protein expression and purification, 140, 52–59. https://doi.org/10.1016/j.pep.2017.08.003 ).
The teachings regarding claim 1 are discussed above. Faris et al. and Zauderer et al. do not teach a heterologous peptide as a part of the composition.
Deng et al. explains that compared to chemical synthesis and extraction from living organisms, heterologous expression of antimicrobial peptides has the advantages of low production cost, short production period, simple extraction, and high yields. Thus, using the motivation from this paper, it would have been obvious to one of ordinary skill in the art to use heterologous peptides, covalently couple it to the first and second therapeutic peptide. and perform the amino and carboxy modifications to maximize cost and yield efficiency.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Faris et al. and Zauderer et al. as applied to claim 1 above, and in further view of Lloyd et al. (US20200283745: published 2020). Lloyd et al. discloses recombinant polypeptides capable of repairing UV-induced DNA damage, reducing the total tumor burden due to UV irradiation, and decreasing the severity of a UV-induced inflammatory response. Lloyd et al. claims “A recombinant polypeptide comprising: a truncated UV damage endonuclease (UVDE), wherein the truncation is amino-terminal (N-terminal) to a conserved region of the UVDE required for enzymatic activity, and at least one heterologous targeting sequence at the carboxv-terminus (C-terminus) of the UVDE” (claim 2). In light of this prior art, it would have been obvious to the inventor to claim a composition comprising of the first therapeutic peptide and/or second therapeutic peptide as a heterologous sequence that is a targeting sequence because Lloyd et al teaches a polypeptide that has a heterologous targeting sequence and Faris et al. and Zauderer et al. teach the first and second therapeutic peptide, respectively.
In addition to previous rejection, claim 8 is also rejected under 35 U.S.C. 103 as being unpatentable over Faris et al. and Zauderer et al. as applied to claim 7 and 8, and in further view of Wooster et al. (US20190085034: published 2019) to reject the subject matter of the “delivery vehicle is a nanoparticle”. Wooster et al. created antibody drug conjugates with a targeting ligand and an anti-cancer agent connected by a linker. The background states: “Nanoparticulate drug delivery systems are attractive for systemic drug delivery because they may be able to prolong the half-life of a drug in circulation, reduce non-specific uptake of a drug, and improve accumulation of a drug at tumors, e.g., through an enhanced permeation and retention (EPR) effect” [See 0004]. Wooster et al. also says that the nanoparticle may be a liposome state that and a protein that may be targeted is the migration and invasion enhancer protein [See 0095]. Therefore, it would have been obvious to a person of ordinary skill using the prior art to make a naturally-derived peptide comprised in delivery vehicle like a nanoparticle to reduce off-target toxicity and improve half-life and efficacy.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Faris et al. (US20020055478A1; published 2002) and Zauderer et al. (US20070081942A1: published 2007) as applied to claim 1 and in further view of Sela et al. (Sela, M. and Zisman, E. (1997), Different roles of D-amino acids in immune phenomena. The FASEB Journal, 11: 449-456. https://doi.org/10.1096/fasebj.11.6.9194525)
Sela et al. states that D-amino acids are more efficacious because “the longer persistence in an undigested form” helps them “resist enzymatic degradation.” It would have been obvious before the effective filing date of the claimed invention to modify the peptides of Faris and Zauderer to arrive at the claimed composition. The artisan of ordinary skill would have been motivated to make the modification with a D amino acid with a reasonable expectation of avoiding proteolytic degradation when used therapeutically as suggested by Sela et al.
Summary
Claims 10-17 are rejected under 135 USC 112(a). Claims 1-17 are rejected under 35 USC 112(b). Claims 1-9 are rejected under 35 USC 103. Claims 10-17 do not have prior art rejections.
Allowable Subject Matter
The following is a statement of reasons for the indication of allowable subject matter: The composition comprising of a six amino acid peptide consisting of an amino acid sequence of LAIA VK, a seven amino acid peptide consisting of an amino acid sequence of RPPCVIL, or a six amino acid peptide consisting of an amino acid sequence of LAIA VK and a seven amino acid consisting of amino acid sequence RPPCVIL.
Conclusion
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/SACHI JAUHARI/ Examiner, Art Unit 1654
/LIANKO G GARYU/ Supervisory Patent Examiner, Art Unit 1654