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 .
Objections/Rejections Withdrawn
Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied, and constitute the complete set presently being applied to the instant application.
Response to Arguments
35 U.S.C. 101
Applicant's arguments filed 8/19/2025 have been fully considered but they are not persuasive. Per Yang et al. (Yang Y, Chen F, Chen HY, Peng H, Hao H, Wang KJ. A Novel Antimicrobial Peptide Scyreprocin From Mud Crab Scylla paramamosain Showing Potent Antifungal and Anti-biofilm Activity. Front Microbiol. 2020 Jul 24;11:1589.), Scyreprocin comprises 84 amino acids (Pg 6, left column, second paragraph). SEQ ID NO 01 is 100% identical to this sequence in terms of both length and sequence identity. Thus, SEQ ID NO 01 is a natural product, not a fragment derived thereof.
Further, no post-translational modifications have been reported that are essential for Scyreprocin function. Thus, much like the countless other eukaryotic proteins expressed in prokaryotic expression systems, there is no reason to expect a functional difference between Scyreprocin derived from Scylla paramamosain and recombinant Scyreprocin.
35 U.S.C. 102
Applicant's arguments filed 8/19/2025 have been fully considered but they are not persuasive. As stated in the previous office action, and reiterated below, the previous claim 1 limitation “is used to inhibit a growth of a cancer cell line” refers to a functional rather than structural element of the instant invention. As such, the claim is being interpreted based upon the structural limitation a peptide SEQ ID NO: 01, wherein the functional limitations recited above are properties endowed by the structure. Thus, Wang anticipates the previous iteration of claims 1-8.
Double patenting
The Applicant’s request that the double patenting rejection be held in abeyance is noted but is maintained herein.
Claim Status
Claims 1-18 are pending under examination. Claims 9-15 were previously withdrawn by the Examiner as non-elected inventions. Claims 16-18 are new. Claims 1-5 are currently amended.
Priority
The Application is the 371 of PCT/CN2019/130620, filed on 12/31/2019. The priority date of 12/31/2019 has been acknowledged.
Claim Interpretation
Claims 1, 3, 5, and 16 each recite a peptide Scyreprocin SEQ ID NO 01 with limitations such “having anti-cancer function” and “inhibits a growth of a cancer cell line” (claim 1) as well as “having a transmembrane function” and “passes through a cell membrane” (claims 3, 5, and 16). These limitations describe functional rather than structural elements of the instant invention. As such, the claims are being interpreted based upon the structural limitation (a peptide that is SEQ ID NO: 1), where the functional limitations are properties endowed by the structure.
Claims 6-8 each recite drug, composition, and therapy, respectively, which are all being interpreted to mean a medicament. Further, the “anti-tumor” nature of the drug, composition, and therapy are being interpreted an intended use.
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 17-18 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.
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, claims 17 and 18 both recite the broad recitation “human cervical cancer, human bladder carcinoma cancer cell line…” (in other words, cancer cell line genera), and the claims also recite “HeLa, T24….” (specific cancer cell line species) which is the narrower statement of the range/limitation. 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. For purposes of examination, claims 17 and 18 have been interpreted to mean the cancer cell line species (i.e., HeLa, T24) instead of the cancer cell line genera.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 16 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 16 is drawn to an amino acid sequence derived from a peptide SEQ ID NO 01 by modification, wherein the amino acid sequence has a transmembrane function and can pass through a cell membrane by diluting the amino acid sequence. The rejection is based on the limitation “an amino acid sequence derived from a peptide SEQ ID NO 01” (emphasis added) which does not disclose sufficient structure-function relationship to meet the written description requirement.
Yang et al. has reported that SEQ ID NO 01 damages microorganism membranes through interactions with various cell surface molecules (Yang Y, Chen F, Chen HY, Peng H, Hao H, Wang KJ. A Novel Antimicrobial Peptide Scyreprocin From Mud Crab Scylla paramamosain Showing Potent Antifungal and Anti-biofilm Activity. Front Microbiol. 2020 Jul 24;11:1589.; see Pg 6-9, “rScyreprocin has multiple antimicrobial mechanisms”). Yang states that some but not all, fragments of SEQ ID NO 01 retain the antimicrobial properties of the full-length SEQ ID NO 01; the examples provided include fragments consisting of residues 20-39 and 40-84 (Pg 6, right column, second paragraph; Table S3 of Yang). Additionally, as evidenced by Alberts belo9w, SEQ ID NO 01 is expected to have an alpha helical structure. Thus, maintaining these structural features of SEQ ID NO 01 is critical in order to also maintain its functional activity. However, the limitations of claim 16 do not indicate any positional information (i.e., from where within SEQ ID NO 01 an amino acid sequence should be derived) or sequence length (i.e., 2 amino acids? 10 amino acids? 80?) to indicate what an amino acid sequence derived from SEQ ID NO 01 would need to retain this function.
Kelly et al. (US 20060058228 A1, published 3/16/2006) discuss a phage display screen to identify peptides that distinguish between well-differentiated (HCT116) and poorly-differentiated (HT29) colon cancer cell lines. Analysis of the selected library resulted in the identification of a nine amino acid, disulfide-constrained peptide having a three amino acid (arg-pro-met, “RPM”) motif that specifically binds HT29 cells ([0032]). Substituting each of RPM with alanine significantly limited or abolished the ability of the peptide to compete with wild type RPM in a binding assay, indicating that these three residues alone accounted for the ability to bind to HT29 cells ([0034]). In contrast to this example, it is unknown which residues of SEQ ID NO 01, within or outside of the sequence encompassed by residues 20-39 and 40-84, impart the membrane-crossing function and, therefore, one cannot extrapolate how to derive such sequences through modification.
Further, Guo (H.H. Guo, J. Choe, & L.A. Loeb, Protein tolerance to random amino acid change, Proc. Natl. Acad. Sci. U.S.A. 101 (25) 9205-9210, (2004).) teaches that a protein’s tolerance to random substitutions ultimately depends on whether the residues at hand are involved the protein’s functional activity. For instance, regions that were highly substitutable in the human DNA repair enzyme 3-methyladenine DNA glycosylase (AAG) include the first 79 N-terminal residues previously demonstrated to be unnecessary for in vitro enzyme activity and DNA binding specificity. In contrast, residues that are involved in glycosylase function or DNA binding did not tolerate amino acid substitutions (“Substitutability and Structure”, Pg 9207-9209; Figure 1). Figure 1 of Guo also indicates that tolerated substitutions are generally conservative, i.e., a nonpolar residue is substituted for another nonpolar residue, etc. However, there are no explicit limitations in the claim that limits the amino acid sequences derived from SEQ ID NO 01.
Applicants have not disclosed any smaller fragments of SEQ ID NO 01.
Consequently, it is unknown whether all amino acid sequences encompassed within SEQ ID NO 01 would retain the structural, chemical, and/or physical properties required to bind to cross a cell membrane. Therefore, the instant specification does not provide adequate written description to possess the broad genus of amino acid sequences derived from SEQ ID NO 01 since the specification does not disclose a correlation between the necessary structure of the sequence and the claimed function to be maintained.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 17 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 17 recites “the cancer cell line is at least one of human cervical cancer cell line (HeLa), human bladder carcinoma cell line (T24), human non-small cell lung cancer cell line (NCI-H460), human prostate cancer cell line (Du145), human liver cancer cell line (HepG2), or human lung fibroblasts (HFLl).” Claim 17 depends from claim 1, which recites that the peptide SEQ ID NO 01 inhibits a growth of a cancer cell line. However, human lung fibroblasts (HFLI) are non-cancerous cells. Thus, claim 17 does not include all the limitations from its parent claim.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-8 and 16-18 are rejected under 35 U.S.C. 101 because they are directed to a judicial exception.
The Supreme Court has given a three-part test for patent eligibility (see flowchart of MPEP 2106(III)):
Are the claims drawn to a process, machine, manufacture, or composition of matter?
2a) If the claims pass the first test, are the claims drawn to a judicial exception (a law of nature, a natural phenomenon (product of nature), or an abstract idea)?
2b) If a judicial exception applies, do the claims recite additional elements that amount to significantly more than the judicial exception?
Applying the three-part test to the instant claims:
Regarding 1), the claims are drawn to a peptide, which is a composition of matter.
Regarding 2a), the peptide claimed is a product of nature.
The claims are drawn to the peptide Scyreprocin (SEQ ID NO 01) or an anti-tumor drug, composition, or therapy comprising it. Several claims include functional limitations, such as SEQ ID NO 01 has anti-cancer function and can inhibit cancer cell growth by diluting the peptide (claims 1, 2, and 17) as well as has transmembrane function and can pass through a cell membrane by diluting the peptide (claims 3-5, 16, and 18).
SEQ ID NO 01 is 100% identical in sequence and in length to Scyreprocin from Scylla paramamosain (UniProt, A0A7D0GB18_SCYPA, 2018). In other words, the naturally-occurring Scyreprocin peptide and the instant SEQ ID NO 01 are indistinguishable from each other. The functional limitations recited above convey attributes endowed by the structure of the peptide itself, and, thus, do not provide significantly more to the naturally-occurring peptide. Additionally, dilution of the peptide still reads on the naturally-occurring peptide.
Regarding 2b), none of the claims above integrate SEQ ID NO 01 into a practical application. At most, the claims recite functional attributes endowed by the structure of SEQ ID NO 01 without significantly more. As such, they do not contain elements added to the judicial exception sufficient to render the claims significantly more than the exception.
Thus, the claims are drawn to patent ineligible subject matter and are rejected here.
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) 1-8 and 16-18 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Wang et al. (US11,512,120 B2, effectively filed 11/21/18), as evidenced by Alberts et al. (Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. Membrane Proteins.).
Wang discloses the peptide Scyreprocin from Scylla paramamosain, which functions as an antimicrobial peptide (Embodiments 3-5, starting at Col. 8, line 45 through Col. 11, line 13; Table 2). Wang describes how natural AMPs exhibit a wide range of activity against various cell types, killing not only microorganisms but also selectively killing tumor cells and some viruses (Col. 1, lines 64-67). Scyreprocin, disclosed by Wang, is the same as the instant SEQ ID NO 01 (Abstract; Col. 7 lines 36-40; Sequencing Listing after Col. 12, SEQ ID NO 01).
Wang further describes a workflow by which cDNA encoding the open reading frame of Scyreprocin (instant SEQ ID NO 01) is amplified through polymerase chain reaction (PCR), inserted into the vector pET28A, expressed in E. coli, and purified (Embodiments 1-2, starting at Col. 5, line 1 through Col. 8, line 44). The resultant recombinant Scyreprocin protein is concentrated, filtered, quantified, diluted to various concentrations between 0.5-32µM, and administered to various microorganism cultures as a method of treatment (Col. 8, lines 35-44; Col. 9, lines 8-13; Embodiments 3-5, Col. 8 line 45 – Col. 11, line 13). Thus, Wang anticipates claims 1 and 2 wherein the peptide Scyreprocin is synthesized using a nucleotide template. Claims 6-8 and 17 are also anticipated. As Scyreprocin is suspended and diluted in a solution intended to treat a disease or be administered, it reads on a drug, composition, and therapy recited in claims 6-8, respectively. Additionally, as Scyreprocin has anti-cancer function and inhibits the growth of cancer cell lines, it would necessarily exert such functions against the cancer cell lines listed in claim 17 (HeLa, T24, NCI-H460, Du145, and HepG2).
Further, secondary structure prediction tools indicate that the Scyreprocin sequence possesses naturally-occurring alpha helices, as indicated by the boxed regions below:
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207
1018
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Greyscale
Alberts teaches that most transmembrane proteins are thought to extend across the bilayer as (1) a single α helix, (2) multiple α helices, or (3) as a rolled-up β sheet (a β barrel; Figure 10-17, enlarged on the final page). Therefore, Wang anticipates the instant claims 3, 4, 5, and 16.
Additionally, claim 18 is also anticipated. As Scyreprocin has transmembrane function and passes through a cell membrane, it would necessarily exert such functions on the cell lines listed in claim 18.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-8 and 16-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 11,512120 B2 (US ‘120). Although the claims at issue are not identical, they are not patentably distinct from each other because they contain overlapping subject matter.
In Sun Pharmaceutical Industries Ltd. v. Eli Lilly and Co., 95 USPQ2d 1797 (Fed. Cir. 2010), the Court determined that Claims of a later patent were held invalid for obviousness-type double patenting when the earlier patent claimed a compound and disclosed its utility in specification, and later patent claimed a method of using compound for use described in specification of earlier patent.
Claim 1 of US ‘120 recites a method for preparing an antimicrobial composition to be used to inhibit growth of microorganisms, wherein the method comprises recombination expression and purification of an antimicrobial peptide Scyreprocin of Scylla paramamosain with a His tag, wherein an amino acid sequence of the antimicrobial peptide Scyreprocin consists of SEQ ID NO 01, and wherein the recombinant expression and purification comprises: cloning an open reading frame of the antimicrobial peptide Scyreprocin of Scylla paramamosain and constructing into a vector pET28A to obtain a recombinant vector; and transferring the recombinant vector to Escherichia coli BL231 to obtain a recombinant expression strain configured to express the antimicrobial peptide Scyreprocin of Scylla paramamosain with a protein purification solution.
Dependent claims include the method wherein the antimicrobial composition is a feed composition (claim 2); and the antimicrobial composition is an anti-mildew and antiseptic composition (claim 3), wherein a “feed” composition and an “anti-mildew and antiseptic” composition are being interpreted as intended uses.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sara E Konopelski Snavely whose telephone number is (571)272-1841. The examiner can normally be reached Monday - Friday 9-6pm EST.
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/SARA E KONOPELSKI SNAVELY/Examiner, Art Unit 1658
/FRED H REYNOLDS/Primary Examiner, Art Unit 1658