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
Examined Herein: 1-16
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 2/14/2023 and 12/24/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings received on 2/14/2023 are accepted.
Claim Rejections - 35 USC § 102
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.
Claims 1-16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kim (Epidermal growth factor (EGF)-based activatable probe for predicting therapeutic outcome of an EGF-based doxorubicin prodrug, 8/29/2020, Journal of Controlled Release, 328:222-236).
With respect to claim 1 and 7, Kim discloses a composition, an EGF-probe, comprising a complex wherein a fluorophore, Cy5.5, and a quencher, BHQ-3, are conjugated on both sides of a peptide, GFLGGKGG, represented by SEQ ID NO 1, which is cleaved by a lysosomal enzyme present in a tumor cell, and EGF is bound to the C-terminal of the peptide, thus meeting the limitations of claim 1 and 7. [Kim, Page 226, Col. 1, Paragraph 4 and Page 227, Figure 2][Kim (Supplementary), Figure S1]
The limitations “…for diagnosing colon cancer or predicting medicinal efficacy” and “…for identifying prognosis for therapeutic effect in a patient with EGFR-positive colon cancer” recite an intended use. The body of claim 1 and 7 fully and intrinsically sets forth all of the limitations of the claimed invention. The aforementioned limitations merely state the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, and does not result in a structural difference between the claimed invention and the prior art. Therefore, the limitations are of no significance to claim construction. MPEP 2111.02(II)
With respect to claim 2, Kim discloses the fluorophore is bound to the N-terminal of the peptide, and the quencher is bound to the ɛ-amino group of a lysine amino acid residue of the peptide, thus meeting the limitations of claim 2. [Kim, Page 227, Figure 2(a)][Kim (Supplementary), Figure S1]
With respect to claim 3, Kim discloses the fluorophore is Cy5.5, thus meeting the limitations of claim 3. [Kim, Page 227, Figure 2(a)][Kim (Supplementary), Figure S1]
With respect to claim 4, Kim discloses the quencher is BHQ3, thus meeting the limitations of claim 4. [Kim, Page 227, Figure 2(a)][Kim (Supplementary), Figure S1]
With respect to claim 5, the limitation “for diagnosing colon cancer [EGFR-positive colon cancer] or predicting medicinal efficacy” recites an intended use. The body of claim 1 fully and intrinsically sets forth all of the limitations of the claimed invention. The aforementioned limitation merely states the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, and does not result in a structural difference between the claimed invention and the prior art. Therefore, the limitation is of no significance to claim construction. MPEP 2111.02(II) Thus, since the limitations of claim 1 have been met, the limitations of claim 5 have also been met.
With respect to claim 6, Kim discloses the complex penetrates into a colon cancer cell and emits fluorescence as it is cleaved by an enzyme existing in the lysosome of the colon cancer cell and quenching by the fluorophore and the quencher is resolved, thus meeting the limitations of claim 6. [Kim, Page 227, Figure 2 and Page 228, Figure 3]
With respect to claim 8, Kim discloses a method comprising treating a sample isolated from a colorectal cancer patient with the EGF-probe, and measuring fluorescence intensity, thus meeting the limitations of claim 8. [Kim, Page 227, Figure 2 and Page 228, Figure 3]
With respect to claim 9, the limitation “wherein the subject is determined as responding to the EGFR drug if the fluorescence intensity is detected” recites a non-limiting description. The limitation does not limit the claim to a particular structure or require particular steps to be performed. Therefore, the claim scope is not limited by this language. MPEP 2111.04(I) Thus, since the limitations of claim 8 have been meet, the limitations of claim 9 have also been met.
With respect to claim 10, Kim discloses a method comprising treating a sample isolated from a colorectal cancer patient who is taking an anticancer drug, doxorubicin, with the EGF-probe, and measuring fluorescence intensity, thus meeting the limitations of claim 10. [Kim, Page 227, Figure 2 and Page 230-231, Figure 5]
With respect to claim 11, the limitation “wherein it is determined that the anticancer drug has no therapeutic effect for the colon cancer patient if the fluorescence intensity is detected” recites a non-limiting description. The limitation does not limit the claim to a particular structure or require particular steps to be performed. Therefore, the claim scope is not limited by this language. MPEP 2111.04(I) Thus, since the limitations of claim 10 have been meet, the limitations of claim 11 have also been met.
With respect to claim 12, Kim discloses a composition comprising:
A complex (EGF probe), wherein a fluorophore, Cy5.5, and a quencher, BHQ3, are conjugated on both sides of a peptide represented by SEQ ID NO 1, which is cleaved by a lysosomal enzyme present in a tumor cell, and EGF (epidermal growth factor) is bound to the C-terminal of the peptide; and
a prodrug complex (EGF Prodrug), wherein EGF and an anticancer drug, doxorubicin, are conjugated on both sides of a peptide represented by SEQ ID NO 1, which is cleaved by a lysosomal enzyme present in a tumor cell, thus meeting the limitations of claim 12. [Kim, Page 231, Col. 2, Paragraph 1, and Page 230-231, Figure 5]
The limitation “for preventing or treating colon cancer” recites an intended use. The body of claim 12 fully and intrinsically sets forth all of the limitations of the claimed invention. The aforementioned limitation merely states the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, and does not result in a structural difference between the claimed invention and the prior art. Therefore, the limitation is of no significance to claim construction. MPEP 2111.02(II)
With respect to claim 13, the limitation “for preventing or treating colon cancer [EGFR-positive colon cancer]” recites an intended use. The body of claim 12 fully and intrinsically sets forth all of the limitations of the claimed invention. The aforementioned limitation merely states the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, and does not result in a structural difference between the claimed invention and the prior art. Therefore, the limitation is of no significance to claim construction. MPEP 2111.02(II) Thus, since the limitations of claim 12 have been meet, the limitations of claim 13 have also been met.
With respect to claim 14-15, Kim discloses the peptide of the prodrug complex and EGF are covalently bonded by a crosslinking agent, sulfo-SMCC, thus meeting the limitations of claim 14 and 15. [Kim, Page 224, Col. 2, Paragraph 2]
With respect to claim 16, Kim discloses the anticancer drug is doxorubicin, thus meeting the limitations of claim 16. [Kim, Page 231, Col. 2, Paragraph 1, and Page 230-231, Figure 5]
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 1-4 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11,618,916 B2 in view of Jiang (US 2005/0107583 A1, Published 5/19/2005) and Kim.
Claims 1-4 of the instant application are drawn to similar limitations of claim 1 of the reference application but differ only by the SEQ ID NO of the peptide. The SEQ ID NO: 1 of the instant application is GFLGGKGG and the SEQ ID NO: 1 of the reference application is GWEHGDK. More specifically, the peptide of the instant application is cleaved by a lysosomal enzyme present in a tumor cell, and the peptide of the reference application is cleaved by a caspase-1 enzyme.
However, Jiang discloses the following compound;
A-X-B-C
Wherein,
C is a cargo moiety, for example, a fluorescent moiety or a fluorescence-quenching moiety,
X is a cleavable linker sequence,
B is a portion that includes basic amino acids, and
A is a portion includes acidic amino acids.
Jiang discloses the intact structure is not significantly taken up by cells; however, upon extracellular cleavage of X, the B-C portion is taken up, delivering the cargo to targeted cells. [Abstract and 0018] Jiang further discloses the cleavable linker may be configured to be cleaved in conditions associated with a particular cell or tissue damage or disease. For examples, for conditions that are normally confined within cells, the cleavable linker may be configured to be cleaved in the presence of intracellular enzymes. More specifically, the cleavable linker may be configured to be cleaved in the presence of a particular enzyme including lysosomal enzymes or caspases. [Jiang, 0020-0021]
Furthermore, Kim discloses GFLGGKGG is a cleavable linker that may be cleaved in the presence of lysosomal enzymes. [Kim, Page 227, Figure 2]
Modifying claim 1 of the reference application by replacing the polypeptide consisting of the amino acid sequence of SEQ ID NO: 1, with the peptide GFLGGKGG, results in the complex of claim 3 and 4 of the instant application.
It would have been obvious to one of ordinary skill in the art to modify claim 1 of the reference application by replacing the polypeptide consisting of the amino acid sequence of SEQ ID NO: 1, with the peptide GFLGGKGG and have a reasonable expectation of success because claim 1 of the reference application is drawn to a complex comprising a cleavable linker, the polypeptide consisting of the amino acid sequence of SEQ ID NO: 1, wherein the linker is cleaved by a caspase-1 enzyme. Jiang also discloses a complex comprising a cleavable linker and further discloses the linker may be configured to be cleaved in conditions associated with a particular cell or tissue damage or disease, such as in the presence of intracellular enzymes, like lysosomal enzymes or caspases. Furthermore, Kim discloses GFLGGKGG is a cleavable linker that may be cleaved in the presence of lysosomal enzymes. So, the reference application discloses a complex comprising a cleavable linker, Jiang discloses such a linker may be configured to cleave in the presence of a lysosomal enzyme or caspase, and Kim discloses GFLGGKGG is the configuration of a linker that may be cleaved in the presence of a lysosomal enzyme. Thus, the combined teachings of the reference application, Jiang, and Kim suggest the cleavable linker disclosed by the reference application may be configured to cleave in the presence of a lysosomal enzyme, by replacing the cleavable linker with GFLGGKGG. Therefore, it is reasonable to expect claim 1 of the reference application may be modified by replacing the peptide with the peptide GFLGGKGG. One would have been motivated to do so to enable the complex of the reference application to be employed for diseases involving lysosomal enzyme mediated cleavage, like colorectal cancer.
Response to Arguments
Applicant's arguments filed 12/3/2025 have been fully considered but they are not persuasive.
Applicant asserts “…the instant application claims the benefit of Korean Patent Application No. 10-2020-0102142, which was filed on August 14, 2020 in the Korean Intellectual Property Office. Certified Copy of Foreign Priority Application was submitted on February 14, 2023. Further, enclosed is an English translation of Korean Patent Application No. 10-2020-0102142, along with a statement from the translator in compliance with 37 CFR 1.55(a) (4) perfecting the foreign priority filing date. As such, it is respectfully submitted that the Applicant has established an effective filing date of August 14, 2020. MPEP 201.15. Applicant respectfully submits that Kim was disclosed on August 29, 2020, which is after the effective filing date of the instant application, which is August 14, 2020. Therefore, Applicant respectfully submits that Kim is disqualified as a prior art reference in accordance with 35 U.S.C. §102(a)(1). [Remarks 12/3/2025, Page 6]
Applicant’s arguments are not persuasive because according to the Bibliographic Data (Bib Data Sheet) the instant application does not claim the benefit of Korean Patent Application No. 10-2020-0102142 or any other foreign application. Therefore, Applicant has not established entitlement to an effective filing date of August 14, 2020. Accordingly, the effective filing date of the instant application is 2/14/2023 and Kim remains a valid prior art reference under 35 U.S.C. §102(a)(1).
Applicant asserts “Indeed, considering numerous types of conditions and enzymes disclosed in Jiang, Jiang's extremely broad disclosure regarding the cleavage of the linker X, Jiang fails to disclose or suggest "SEQ ID NO 1, which is cleaved by a lysosomal enzyme present in a tumor cell," as recited in claim 1.” [Remarks 12/3/2025, Page 10; see also remarks on page 9]
Applicant’s arguments are not persuasive because they attack Jiang as an individual reference, though the instant rejection relies on the combination of the reference application, Jiang, and Kim. One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Accordingly, in view of the combined teachings of the reference application, Jiang, and Kim, the Office maintains that it would have been obvious to a POSITA to modify claim 1 of the reference application by replacing the polypeptide consisting of the amino acid sequence of SEQ ID NO: 1, with the peptide GFLGGKGG for the reasons set forth in the OA of 9/23/2025. Moreover, Applicant’s reliance on MPEP 2144.08 is misplaced because the instant rejection does not rely on an “obvious to try” rationale.
Oath/Declaration
The declaration under 37 CFR 1.132 filed 12/3/2025 insufficient to overcome the rejection of the instant claims based upon 35 U.S.C 102(a)(1) as set forth in the last Office action because the declaration does not establish entitlement to an effective filing date of August 14, 2020. The declaration submits an English translation of Korean Patent Application No. 10-2020-0102142, along with a statement from the translator and alleges the submission perfects the foreign priority filing date. However, according to the Bibliographic Data (Bib Data Sheet) the instant application does not claim the benefit of Korean Patent Application No. 10-2020-0102142 or any other foreign application. Accordingly, the effective filing date of the instant application is 2/14/2023.
Conclusion
THIS ACTION IS MADE FINAL. 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.
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/K.A.C./Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618