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 .
This rejection is Non-Final rejection because new ODP rejections.
Claim Status
Claims 1-14 are pending.
Claims 1-14 have been examined.
Priority
This application is a CON of 17/737,008 05/04/2022 ABN
17/737,008 has PRO 63/329,321 04/08/2022
17/737,008 has PRO 63/184,198 05/04/2021
Information Disclosure Statement
No IDS of record
Withdrawn Objection and Rejection
The objection of claim 1, 4-5 , 8, and 13-14 are objected to is withdrawn because the claim amendments overcome the objection.
The rejection of claim 6 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn because the amendment to claim 6 overcomes the rejection.
Maintained Rejection
Claim Rejections - 35 USC § 103
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.
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.
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.
1. Claims 1-5, 7-8, and 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over the printed document NCT03517176 (last update posted 2018-05-07 shown at page 4, previously cited 5/7/2025) in view of Lam et al. (US 9,073,974 B2, previously cited 5/7/2025) and Ruoslahti et al. (EP 2445536 B2, previously cited 5/7/2025).
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Claim 1 is drawn to a method for treating, inhibiting, or reducing the volume of a tumor of a pancreatic cancer in a subject or patient in need thereof, wherein the method comprises simultaneous, separate or sequential administration of (i) a cyclic peptide corresponding to the chemical structure (synonym of CEND-1 and iRGD) in a range of 0.2-3.2 mg/kg body weight/day or per dose of chemotherapy with a combination of (ii) nabpaclitaxel in a range of 120-130 mg/m2, and (iii) gemcitabine in a range of 900-1100 mg/m2.
NCT03517176 teaches CEND-1 in combination with Nabpaclitaxel and Gemcitabine in Metastatic Pancreatic Cancer (Title). NCT03517176 teaches CEND-1 dose levels, first as a monotherapy (during 1-week run-in), followed by combination therapy with nabpaclitaxel and gemcitabine (p5, Detailed Description, para 3), reading on sequential and/or simultaneous administration. NCT03517176 teaches nab-paclitaxel at the dose of 125mg/m2 (p6, Arms), reading on the limitation (ii). NCT03517176 further teaches gemcitabine at the dose of 1000mg/m2 (p7, Arms), reading on the limitation (iii). The specification defines CEDG-1 (Fig 2 as the claimed structure) as an iRGD compound with CAS Registry#: 2580154-02-3 [0026]. Thus, NCT03517176’s CEND-1 is the same compound of CAS Registry#: 2580154-02-3 as claimed.
Lam et al. teach the use of cyclic RGD-containing peptide linked via disulfide bond as a diagnostic and/or therapeutic agent (abstract; col 3, line 60-66). Lam et al. teach a cyclic RGD-containing peptide can be administered at the same time, just prior to or just after the administration of a second, e.g., anti-cancer agent (col 5, line 56-65), reading on simultaneous, separate or sequential administration of an anti-cancer agent. Lam et al. teach a treated cancer is pancreatic cancer (col 22, line 17). Lam et al. teach the dosages of cyclic RGD-containing peptide, however, may be varied depending upon the requirements of the patient, the severity of the condition being treated, and the compound being employed. Determination of the proper dosage for a particular situation is within the skill of the practitioner. Generally, treatment is initiated with smaller dosages which are less than the optimum dose of the compound. Thereafter, the dosage is increased by small increments until the optimum effect under circumstances is reached. For convenience, the total daily dosage may be divided and administered in portions during the day, if desired (col 19, line 13-15 and 24-31). Lam et al.
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suggest the cyclic RGD-containing peptide compound can be optimized from 0.1 mg/kg to about 200 mg/kg (col 19, line 11). Furthermore, Ruoslahti et al. is cited to show iRGD at a dosage of 1 mg/kg and 3 mg/kg sufficient to enhance efficacy of a co-administered anticancer drug shown as follows (Fig 15). Ruoslahti et al. further teach an iRGD is a cyclic RGD peptide [0313, 0424], consistent with NCT03517176 and Lam et al.
Because (a) NCT03517176 teaches determination of CEND-1 (a cyclic RGD-containing peptide of iRGD) dose by clinical trials (p5, Detailed Description, para-3), (b) Lam et al. suggest a cyclic RGD-containing peptide compound can be optimized from 0.1 mg/kg to about 200 mg/kg (col 19, line 11), and (c) Ruoslahti et al. is further cited to show an very active iRGD peptide (e.g., a cyclic peptide of CRGDK/RGPD/EC; SEQ ID NO:61) is effective at a dose of 1 mg/kg and 3 mg/kg known in the art [Fig 15], one of ordinary skill in the art before the effective filing date of this invention would have either at once envisage of using Ruoslahti’s dose of iRGD at 1 or 3 mg/kg for another vary active iRGD compound of CEND-1 or found it obvious to optimize the active CEND-1 compound starting with Lam’s lower dose of 0.1 mg/kg, 0.2 mg/kg, 0.5 mg/kg, 1 mg/kg, 2 mg/kg, or 3.5 mg/kg until the optimum effect under circumstances is reached as suggested by Lam et al. and Ruoslahti et al., reading on the limitation (i).
One of ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine NCT03517176 with a dosage range of a cyclic RGD-containing peptide for cancer therapy taught by Lam et al. in view of Ruoslahti et al. because (a) NCT03517176 teaches determination/optimization of CEND-1 (a cyclic RGD-containing peptide of iRGD) dose by clinical trials (p5, Detailed Description, para-3) in a combination for cancer therapy, (b) Lam et al. teach determination of the proper dosage of the administered cyclic RGD-containing peptide compound for a particular situation is within the skill of the practitioner. Generally, treatment is initiated with smaller dosages and the dosage is increased by small increments until the optimum effect under circumstances is reached (col 19, line 13-15 and 24-31). Lam et al. further suggest the dose of a cyclic RGD-containing peptide compound can be optimized from 0.1 mg/kg to about 200 mg/kg (col 19, line 11), and (c) Ruoslahti et al. explicitly show an iRGD at a dose of 1 or 3 mg/kg suitable to promote efficacy of a co-administered anticancer agent [0012]. The combination would have reasonable expectation of success because all references teach co-administration of a cyclic RGD-containing peptide (e.g., iRGD) with one or more anti-cancer agents to treat pancreatic cancer (Title of NCT03517176; Lam et al. col 22, line 17; and Ruoslahti et al. [0421]).
With respect to claims 2-3, NCT03517176 teaches a protocol designed to evaluate the safety, tolerability, and biologic activity of CEND-1 in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) who are undergoing combination therapy with nabpaclitaxel and gemcitabine (p5, Detailed Description, para 2). NCT03517176 did not exclude treatment of a particular stage of pancreatic ductal adenocarcinoma, demonstrating the combination able to treat patients at any stage of pancreatic ductal adenocarcinoma (0-IV).
With respect to claim 4, NCT03517176 teaches patients will receive an IV bolus of CEND-1 on Day 1 of the 1-week run-in period followed by one treatment cycle (28 days) with the CEND-1 / nabpaclitaxel(125mg/m2) / gemcitabine (1000mg/m2) combination given on days 1, 8, and 15 (p6, col 1, Arms to p7, col 1), reading on once weekly.
With respect to claim 5, NCT03517176 teaches CEBD-1/iRGD administrated via intravenous (IV) injection (p6, col 2, Assigned Inventions), reading on CEBD-1/iRGD suspended in a biocompatible medium suitable for IV injection.
With respect to claim 6, Ruoslahti et al. teach a combination of iRGD and anticancer drug are injected intravenously in PBS, phosphate buffered saline, [0434].
With respect to claim 7, NCT03517176 teaches CEBD-1/iRGD administrated via intravenous (IV) injection (p6, col 2, Assigned Inventions).
With respect to claim 8, Lam et al. further suggest the dose of a cyclic RGD-containing peptide compound can be optimized from 0.1 mg/kg to about 200 mg/kg (col 19, line 11). Ruoslahti et al. show a single dose of 1 or 3 mg/kg is suitable for iRGD as a therapeutic agent (Fig 15). NCT03517176 teaches nab-paclitaxel at the dose of 125mg/m2 (p6, Arms) and gemcitabine at the dose of 1000mg/m2 (p7, Arms).
With respect to claims 13-14, NCT03517176 teaches CEND-1 in combination with Nabpaclitaxel and Gemcitabine in metastatic pancreatic cancer (Title). NCT03517176 teaches CEND-1 is a tumor penetrating peptide, scientifically also known as iRGD, (p5, Detailed Description, para-2). Lam et al. teach the dosages of cyclic RGD-containing peptide, however, may be varied depending upon the requirements of the patient, the severity of the condition being treated, and the compound being employed. Determination of the proper dosage for a particular situation is within the skill of the practitioner. Ruoslahti et al. explicitly show an effective dose of an iRGD peptide can be 1 mg/kg or 3 mg/kg, (Fig 15) and a slightly higher dose at 4 µmol/kg (about 3.96 mg/kg CEND-1, a MW of 989.1) [0438]. Thus, one of ordinary skill in the art would have found it obvious to further optimize the iRGD of NCT03517176’s CEND-1 in a very narrow dosage range between 1 mg/kg and 3.96 mg/kg as suggested by Ruoslahti et al. The specification disclosed iRGD-analog CEND-1 is administered in a broader range amount selected from 0.01-100, 0.19-4 mg/kg per dose [0020], demonstrated that the entire optimization range from 1 mg/kg to 4 mg/kg of CEND-1 is effective in a combination therapy. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05 (I).
NCT035 l 7176 merely reflects a proposal for clinical investigation without disclosing efficacy, specific dosing, or treatment results. NCT03517176 "does not specify a dose of administered CEND-1." It is respectfully submitted that those of skill in the art, at the time of Applicant's disclosure, would have been unsure and uncertain, that Applicant's claimed method would have worked (Remarks, p7, para 2-3).
Lam does not teach any information regarding the specific cyclic peptide having the configuration. Ruoslahti does not teach any information regarding the specific cyclic peptide having the configuration required in claim 1. The cited combination of prior art, including the cited clinical trial, merely represents an unproven proposal or ongoing investigation, the skilled artisan would not have had a reasonable expectation of success based on such speculative disclosure of each prior art reference, either taken alone, or in combination.
Response to Arguments
Applicant's arguments filed 11/7/2025 have been fully considered but they are not persuasive for the reasons as follows.
Applicant’s argument (i) is not illogical because one would have reasonable expectation of success before submitting a treatment protocol to FDA. NCT035 l 7176 provides detailed patient eligibility of inclusion and exclusion criteria (p9-10). NCT035 l 7176 provides dosages of known anti-cancer compounds nab-paclitaxel at the dose of 125mg/m2 (p6, Arms) and gemcitabine at the dose of 1000mg/m2 (p7, Arms) in combination with CEND-1. NCT035 l 7176 further teach this clinical trial is for ascending dose levels of CEND-1 (optimization of dose level of CEND-1) in combination with gemcitabine and nab-paclitaxel (p6, Arm) demonstrating reasonable expectation of success before submitting a treatment protocol to FDA. Furthermore, Lam et al. and Ruoslahti et al. are cited to demonstrate a combination of an iRGD, functionally equivalent to CEND-1, and other anti-cancer agents to treat cancer with expected success. When the reference relied on expressly anticipates or makes obvious all of the elements of the claimed invention, the reference is presumed to be operable. See MPEP 2121(I).
Applicant’s argument (ii) is not persuasive because prior art references do not need FDA approval and a prior art reference is presumed to be operable (See MPEP 2121(I)). Both Lam et al. and Ruoslahti teach an effective amount of iRGD, functionally equivalent to CEND-1, can be determine by routine optimization descried above not repeated here. NCT035 l 7176 teach ascending dose levels of CEND-1 (optimization of dose level of CEND-1) in combination with gemcitabine and nab-paclitaxel (p6, Arm) consistent with Lam et al. and Ruoslahti et al.. The treatment effect as argued by applicant is not found in claims. Furthermore, the argued treatment effect is a result effective variable which can be optimized under prior art conditions through routine optimization. In particular, Ruoslahti et al. suggest a functionally equivalent compound of iRGD at a dosage of 1 mg/kg or 3 mg/kg is sufficient to enhance efficacy of a co-administered anticancer drug (Fig 15).
2. Claims 9-12 are rejected under 35 U.S.C. 103 as being unpatentable over the printed document NCT03517176 in view of Lam et al. and Ruoslahti et al. as applied to claims 1-5, 7-8, 13-14 and further in view of Von Hoff et al. (N Engl J Med 2013;369:1691-703, previously cited 5/7/2025).
Claim 9 is drawn to the method is measured by determining Overall Response Rate (ORR), Progression Free Survival (PPS) and/or Overall Survival (OS).
NCT03517176 in view of Lam et al. and Ruoslahti et al. teach a combination therapy comprising (i) 1 mg/kg to 4 µmol/kg of CEND-1 (e.g., 1 or 3 mg/kg taught by Ruoslahti’s Fig 15), (ii) nab-paclitaxel at the dose of 125mg/m2 (NCT03517176 p7, Experimental B) and (iii) gemcitabine at the dose of 1000mg/m2 (NCT03517176 p7, Experimental B) to treat pancreatic cancer.
NCT03517176 does not teach a criteria of measurement after treatment.
Similarly, Von Hoff et al. teach “Increased Survival in Pancreatic Cancer with nab-Paclitaxel plus Gemcitabine” (Title). Von Hoff et al. teach patients received the study treatment until disease progression. The primary end point was overall survival; secondary end points were progression-free survival and overall response rate (p1691, Abstract-Methods), reading on claim 9.
With respect to claim 10-12, NCT03517176 teaches a combination therapy comprising nab-paclitaxel at the dose of 125mg/m2, gemcitabine at the dose of 1000mg/m2 and an iRGD peptide CNED-1 to treat pancreatic cancer (NCT03517176 p7, Experimental B). Ruoslahti et al. is further cited to show that a functionally equivalent iRGD peptide needs to be administered in 1 mg/kg or 3 mg/kg (Fig 15), reading on administered iRGD at a dose of 1 or 3 mg/kg known in the art.
Response to Arguments
Applicant's arguments filed 11/7/2025 have been fully considered but they are not persuasive. See response to arguments at pages 9-10 above.
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 1-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5-6 of U.S. Patent No. 8,367,621 B2 (the ‘621 patent) in view of NCT03517176, Lam et al., Ruoslahti et al., and Von Hoff et al.
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Claim 1 of the ‘621 patent disclosed an isolated peptide of SEQ ID NO: 1 consisting of the peptide sequence shown as follows. The specification of the ‘621 patent defines the peptide of SEQ ID NO: 1 as an iRGD peptide (col 9, line 20-21; Fig 24) consisting of the same primary amino acid sequence of CEND-1.
Claims 5-6 of the ‘621 patent disclosed the isolated SEQ ID NO: 1 is cyclized via disulfide bond, substantially the same as cyclic CEND-1.
Claims 1 and 5-6 of the ‘621 patent do not disclose administration of the cyclic peptide (iRGD) in a combination therapy.
The relevancy of NCT03517176 in view of Lam et al., Ruoslahti et al., and Von Hoff et al. teach a combination therapy comprising CEND-1 (1-4 mg/kg) / nabpaclitaxel (125mg/m2) / gemcitabine 1000mg/m2 to treat pancreatic cancer as applied to claims 1-14 described above not repeated here.
Because NCT03517176 teaches beneficial use of CEND-1 as a tumor penetrating peptide (scientifically also known as iRGD) that activates a drug transport mechanism in a combination with nabpaclitaxel (125mg/m2) and gemcitabine 1000mg/m2 to treat pancreatic cancer, one of ordinary skill in the art would have found it obvious to use the cyclic peptide of iRGD taught by claims 1 and 5-6 of the ‘621 patent with NCT03517176 in view of Lam et al. in view of Ruoslahti et al., and Von Hoff et al. to treat pancreatic cancer.
Thus, claims 1 and 5-6 of the ‘621 patent in view of NCT03517176, Lam et al., Ruoslahti et al., and Von Hoff et al. are obvious to the instant claims 1-14.
Applicant’s Argument
None of the cited references teach the instant compound of CEND-1 (Fig 2 as the claimed structure; CAS Registry#: 2580154-02-3) as claimed (Remarks, p9, last para to p10, para 1).
Response to Arguments
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Applicant's arguments filed 11/07/2025 have been fully considered but they are not persuasive because claims 1 and 5-6 of the ‘621 patent disclosed a cyclic iRGD peptide consisting of the primary sequence of CEND-1 as follows. NCT03517176 teaches beneficial use of CEND-1 comprising acetylation and amidation at the side chain of cysteine residues as a tumor penetrating peptide (scientifically also known as iRGD) that activates a drug transport mechanism in a combination with nabpaclitaxel (125mg/m2) and gemcitabine 1000mg/m2 to treat pancreatic cancer. Thus, the combined references teach the instant compound structure.
Claims 1-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5-6 of U.S. Patent No. 9,115,170 B2 (the ‘170 patent) in view of NCT03517176 in view of Lam et al. in view of Ruoslahti et al., and Von Hoff et al.
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Claim 1 of the ‘170 patent disclosed an isolated peptide of SEQ ID NO: 1. The specification of the ‘170 patent defines the peptide of SEQ ID NO: 1 as an iRGD peptide shown as follows (col 10, line 19-20).
Claims 5-6 of the ‘170 patent disclosed the isolated SEQ ID NO: 1 is cyclized via a disulfide bond.
The relevancy of NCT03517176 in view of Lam et al., Ruoslahti et al., and Von Hoff et al. teach a combination therapy comprising CEND-1 (1-4 mg/kg) / nabpaclitaxel (125mg/m2) / gemcitabine 1000mg/m2 to treat pancreatic cancer as applied to claims 1-14 described above not repeated here.
Because NCT03517176 teaches beneficial use of CEND-1 as a tumor penetrating peptide (scientifically also known as iRGD) that activates a drug transport mechanism in a combination with nabpaclitaxel (125mg/m2) and gemcitabine 1000mg/m2 to treat pancreatic cancer, one of ordinary skill in the art would have found it obvious to use the cyclic peptide of iRGD taught by claims 1 and 5-6 of the ‘170 patent with NCT03517176 in view of Lam et al. in view of Ruoslahti et al., and Von Hoff et al. to treat pancreatic cancer.
Thus, claims 1 and 5-6 of the ‘176 patent in view of NCT03517176 in view of Lam et al. in view of Ruoslahti et al., and Von Hoff et al. are obvious to the instant claims 1-14.
Response to Arguments
Applicant's arguments filed 11/07/2025 have been fully considered but they are not persuasive. See response to argument of rejecting the ‘621 patent above.
Claims 1-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11-16, 18-19, and 21-23 of copending Application No. 17/923,408 (the ‘408 application 9/22/2023). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘408 application disclosed a method substantially the same to the instant claimed method.
Claim 14 of the ‘408 application disclosed a method of treating pancreatic cancer in a patient in need thereof, comprising administering to the patient an effective amount of CEND-1 (synonym of CAS Registry#: 2580154-02-3), in combination with gemcitabine and/or nab-paclitaxel, or pharmaceutically acceptable salts thereof. Claim 21 of the ‘408 application disclosed CEND-1 is administered in a range of 0.2-3.2 mg/kg body weight/day or per dose of chemotherapy; nabpaclitaxel is administered at 125 mg/m2; and gemcitabine is administered at 1000 mg/m2.
Thus, claim 14 in view of claim 21 of the ‘408 application is obvious to the instant claim 1.
Claim 15 of the ‘408 application disclosed the treated pancreatic cancer is selected from the group consisting of: primary pancreatic cancer, metastatic pancreatic cancer, refractory pancreatic cancer, cancer drug resistant pancreatic cancer and adenocarcinoma, satisfying the instant claim 2.
Claim 16 of the ‘408 application disclosed the treated cancer is ductal adenocarcinoma (Stage 0-IV), satisfying the instant claim 3.
Claim 19 of the ‘408 application disclosed regimen of CEND-1 (synonym of CAS Registry#: 2580154-02-3) from 4 times/day to once a week, satisfying the instant claim 4.
Claim 11 of the ‘408 application disclosed CEND-1 is present in a dry formulation or suspended in a biocompatible medium, satisfying the instant claim 5.
Claim 12 of the ‘408 application disclosed the biocompatible medium is selected from the group consisting of: water, buffered aqueous media, saline, buffered saline, satisfying the instant claim 6.
Claim 13 of the ‘408 application disclosed CEND-1 is administered intravenously, satisfying the instant claim 7.
Claim 21 of the ‘408 application disclosed CEND-1 is administered in a range of 0.2-3.2 mg/kg body weight/day or per dose of chemotherapy; nabpaclitaxel is administered at 125 mg/m2; and gemcitabine is administered at 1000 mg/m2, satisfying the instant claim 8.
Claim 22 of the ‘408 application disclosed efficacy or clinical activity of the method is measured by determining: Overall Response Rate (ORR), Progression Free Survival (PFS) and/or Overall Survival (OS), satisfying the instant claim 9.
Claim 23 of the ‘408 application disclosed efficacy or clinical activity of the method is measured by determining (a) Overall response rate > 25% ~ 95%, (b) Progression Free Survival > 25% ~ 95%, and/or (c) Overall Survival > 25% ~ 95%, satisfying the instant claims 10-12 respectively.
Claim 18 of the ‘408 application disclosed CEND-1 is administered in an amount corresponding to 3.2 mg/kg body weight/per dose of cancer therapy, satisfying the instant claim 13-14.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant's arguments filed 11/7/2025 have been fully considered but they are not persuasive because the request of this provisional rejection held in abeyance does not overcome the provisional ODP rejection of record.
New ground of ODP Rejection.
Claims 1-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5-6 of U.S. Patent No. 12,351,653 B1 (the ‘653 patent) in view of NCT03517176, Lam et al., Ruoslahti et al., and Von Hoff et al.
Claim 1 and 6 of the ‘653 patent disclosed a cyclic compound structure of CEND-1.
Claim 5 of the ‘653 patent disclosed a combination of CEND-1 together with an anticancer agent.
Claim 1 and 5-6 of the ‘653 patent do not specify a specific anticancer compound used together with CEND-1.
The relevancy of NCT03517176 in view of Lam et al., Ruoslahti et al., and Von Hoff et al. teach a combination therapy comprising CEND-1 (1-4 mg/kg) / nabpaclitaxel (125mg/m2) / gemcitabine 1000mg/m2 to treat pancreatic cancer as applied to claims 1-14 described above not repeated here.
Because NCT03517176 teaches beneficial use of CEND-1 as a tumor penetrating peptide (scientifically also known as iRGD) that activates a drug transport mechanism in a combination with nabpaclitaxel (125mg/m2) and gemcitabine 1000mg/m2 to treat pancreatic cancer, one of ordinary skill in the art would have found it obvious to use the cyclic peptide of iRGD taught by claims 1 and 5-6 of the ‘653 patent with NCT03517176 in view of Lam et al., Ruoslahti et al., and Von Hoff et al. to treat pancreatic cancer.
Thus, claims 1 and 5-6 of the ‘653 patent in view of NCT03517176, Lam et al., Ruoslahti et al., and Von Hoff et al. are obvious to the instant claims 1-14.
Claim 1-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 19/248,341 (the ‘341 application 9/22/2023) in view of NCT03517176 in view of Lam et al. in view of Ruoslahti et al., and Von Hoff et al.
Claim 1 of the ‘341 application disclosed a method of synthesizing the compound of CEND-1 with nab-paclitaxel and gemcitabine.
The relevancy of NCT03517176 in view of Lam et al. in view of Ruoslahti et al., and Von Hoff et al. teach a combination therapy comprising CEND-1 (1-4 mg/kg) / nabpaclitaxel (125mg/m2) / gemcitabine 1000mg/m2 to treat pancreatic cancer as applied to claims 1-14 described above not repeated here.
Because NCT03517176 teaches beneficial use of CEND-1 as a tumor penetrating peptide (scientifically also known as iRGD) that activates a drug transport mechanism in a combination with nabpaclitaxel (125mg/m2) and gemcitabine 1000mg/m2 to treat pancreatic cancer, one of ordinary skill in the art would have found it obvious to use the cyclic peptide of iRGD taught by claim 1 of the ‘341 application with NCT03517176 in view of Lam et al. in view of Ruoslahti et al., and Von Hoff et al. to treat pancreatic cancer.
Thus, claim 1 of the ‘341 application in view of NCT03517176 in view of Lam et al. in view of Ruoslahti et al., and Von Hoff et al. are obvious to the instant claims 1-14.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowed.
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/J.L/Examiner, Art Unit 1658
26-November-2025
/LI N KOMATSU/ Primary Examiner, Art Unit 1658