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 .
Priority
The instant application, filed on 08/04/2023, claims domestic benefit to U.S. provisional application no. 63/370,524, filed on 08/05/2022.
Status of Claims/Application
Applicant’s amendment and remarks, dated 02/10/2026, is acknowledged.
Claims 1, 5, 7, and 9 have been amended.
Claims 4, 6, and 10 – 13 have been cancelled.
No new claims have been added.
Claims 1 – 3, 5, and 7 – 9 are currently pending and are examined on the merits herein.
Rejections Withdrawn
Applicant’s amendments and arguments, filed 02/10/2026, with respect to the rejection of claims 1 - 13 under 35 U.S.C. 112(a), as failing to comply with the enablement requirement, has been fully considered and is persuasive. Claim 1 has been amended by replacing the word “treating” which encompassed prevention, with “the curative or palliative treatment”. The rejection is hereby withdrawn.
Applicant’s amendments and arguments, filed 02/10/2026, with respect to the rejection of claims 1 – 4, 7, 8, 10, 11, and 13 under 35 U.S.C. 102(a)(1) as being anticipated by Eskouhie Tchaparian, Louis Lin (Evaluation of antitumor efficacy of CA102N, H-Nim and hyaluronic acid(HA)conjugate, alone or in combination with 5-fluorouracil (5-FU) in in vivo human colorectal cancer models[abstract] Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia(PA):AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5811) (IDS 08/30/2025) has been fully considered and is persuasive. As claims 4, 10, 11, and 13 are cancelled, the claim rejections are withdrawn. Claim 1 has been amended to include the limitations of the original claims 6 and 12. The original claims 6 and 12 were not rejected over the above reference under 35 U.S.C. 102(a)(1) as being anticipated. The rejection is hereby withdrawn.
Applicant’s amendments and arguments, filed 02/10/2026, with respect to the rejection of claims 1 – 3, 5, 9, and 10 under 35 U.S.C. 102(a)(1) as being anticipated by (First-in-human Study of CA102N Monotherapy and CA102N Combined With Trifluridine/Tipiracil (LONSURF) in Subjects With Advanced Solid Tumors, https://clinicaltrials.gov/study/NCT03616574, first started on 4/9/2019) (IDS 10/02/2024) has been fully considered and is persuasive. Claim 1 has been amended to recite 5-fluorouracil as the fluoropyrimidine in the pharmaceutical composition. Claim 10 is cancelled. The rejection is hereby withdrawn.
Applicant’s amendments and arguments, filed 02/10/2026, with respect to the rejection of claims 1 – 5, 7, 10, and 11 under 35 U.S.C. 103 as being unpatentable over Jian,Y et al ((2017) Hyaluronic acid–nimesulide conjugates as anticancer drugs against CD44-overexpressing HT-29 colorectal cancer in vitro and in vivo, International Journal of Nanomedicine, 2315-2333) (IDS 10/02/2024) in view of Lee et al ((2019) Tumor mutation burden and prognosis in patients with colorectal cancer treated with adjuvant fluoropyrimidine and oxaliplatin, Clin Cancer Res, 25:6141-7) (PTO-892 01/28/2026), and Sochacka-Cwikla et al ((2022) FDA-Approved drugs for hematological malignancies – the last decade review, Cancers 2022, 14, 87) (PTO-892 01/28/2026) has been fully considered and is persuasive. Claims 4, 10, and 11 have been cancelled. Claim 1 is amended to include limitations of the original claims 6 and 12, which were not rejected over the above references. The rejection is hereby withdrawn.
Applicant’s amendments and arguments, filed 02/10/2026, with respect to the rejection of claim 3 under 35 U.S.C. 103 as being unpatentable over Jian,Y et al ((2017) Hyaluronic acid–nimesulide conjugates as anticancer drugs against CD44-overexpressing HT-29 colorectal cancer in vitro and in vivo, International Journal of Nanomedicine, 2315-2333) (IDS 10/02/2024), Lee et al ((2019) Tumor mutation burden and prognosis in patients with colorectal cancer treated with adjuvant fluoropyrimidine and oxaliplatin, Clin Cancer Res, 25:6141-7) (PTO-892 01/28/2026), and Sochacka-Cwikla et al ((2022) FDA-Approved drugs for hematological malignancies – the last decade review, Cancers 2022, 14, 87) (PTO-892 01/28/2026), as applied to claims 1 – 5, 7, 10, and 11 above, and further in view of Tomaz et al ((2022) Molecular characterization of a first-in-human clinical response to nimesulide in acute myeloid leukemia, Front. Oncol. 12:874168) (IDS 10/02/2024) has been fully considered and is persuasive. Claims 4, 10, and 11 have been cancelled. Claim 1 is amended to include limitations of the original claims 6 and 12, which were not rejected over the above references. The rejection is hereby withdrawn.
Applicant’s amendments and arguments, filed 02/10/2026, with respect to the rejection of claims 1, 4, 6, and 10 – 12 under 35 U.S.C. 103 as being unpatentable over Eskouhie Tchaparian, Louis Lin (Evaluation of antitumor efficacy of CA102N, H-Nim and hyaluronic acid(HA)conjugate, alone or in combination with 5-fluorouracil (5-FU) in in vivo human colorectal cancer models[abstract] Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia(PA):AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5811) (IDS 08/30/2025) has been fully considered. Claims 4, 6, and 10 – 12 have been cancelled. Claim 1 is amended to include the limitations of the original claims 4, 6, and 10 – 12. The rejection is updated, and presented below.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1 – 3, 7, and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Eskouhie Tchaparian and Louis Lin, Cancer Res 2018;78(13 Suppl):Abstract nr 5811 (IDS 08/30/2025).
Tchaparian teaches that the combination of CA102N and 5-FU represents a promising potential therapeutic strategy in the treatment of colorectal cancer. It teaches that the combination therapy displayed a marked reduction in tumor growth and that the drug combination displayed a synergistic antitumoral effect in HT29 Xenograft mice models. It teaches the intravenous administration of CA102N with the dosage 200mg/kg administered twice a week (BIW)(i.v. 200mg/kg, BIW), and also with the dosage 400mg/kg administered once a week(QW). It also teaches the intravenous administration of 5-FU with the dosage 50mg/kg, once a week(i.v. 50mg/kg, QW). It teaches the treatment period as 21 days.
Tchaparian teaches the dosage of HA-nimesulide conjugate as 200 mg/kg and 400 mg/kg. It also teaches the dosage of 5-FU as 50 mg/kg.
Tchaparian does not teach the dosage of 5 to 150 mg/kg/dose of hyaluronan-nimesulide conjugate , and the dosage of 1 to 30 mg/kg/dose of 5-FU limitation in the amended claim 1.
However, it would have been prima facie obvious for one of ordinary skill in the art to modify the dosages to determine the therapeutically effective amount for each of the components in the pharmaceutical composition. One of ordinary skill in the art would have a reasonable expectation of success because it is routine to adjust the dosage by the body weight of the subject in need of such a therapeutic.
Regarding claim 3, as it does not expressly limit the tumor of claim 2 to liquid tumor, but is merely limiting the Markush of liquid tumors to those recited, Tchaparian teaching a solid tumor as recited in claim 2 would also meet the limitation of claim 3.
Regarding claim 7, Tchaparian teaches the once per week (QW), and twice per week (BIW) administration of CA102N.
Regarding claim 8, the treatment period of 21 days falls within the claim limitation “from about two weeks to about four weeks”.
Thus, instant claims 1 – 3, 7, and 8 are rejected by the teachings of Tchaparian.
Claims 5 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Eskouhie Tchaparian and Louis Lin, Cancer Res 2018;78(13 Suppl):Abstract nr 5811 (IDS 08/30/2025) as applied to claims 1 – 3, 7, and 8 above, and further in view of First-in-human Study of CA102N Monotherapy and CA102N Combined With Trifluridine/Tipiracil (LONSURF) in Subjects With Advanced Solid Tumors, https://clinicaltrials.gov/study/NCT03616574, first started on 4/9/2019 (IDS 10/02/2024).
Tchaparian’s teachings are as discussed above.
Tchaparian’s teachings differ from the instantly claimed invention in that Tchaparian does not teach that the hyaluronan-nimesulide conjugate is administered at 0.1 to 3.2 mg/kg/dose of nimesulide equivalents, and that the hyaluronan-nimesulide conjugate is administered twice of a treatment period of 28 days.
ClinicalTrial (Detailed description) teaches the first-in-human study of CA102N monotherapy and of CA102N combined with trifluridine/tipiracil (LONSURF®) in subjects with advanced or metastatic solid tumors. It also teaches the application of the combination therapy in subjects with metastatic colorectal cancer. It teaches the dosage of CA102N as 0.36, 0.54, and 0.72 mg/kg of nimesulide equivalents on days 1 and 15 of a 28-day cycle (Arms and Interventions) and LONSURF® dosage as 35 mg/m2/dose orally twice daily on days 1 through 5 and days 8 through 12 of each 28-day cycle.
It would have been obvious to combine Tchaparian and ClinicalTrial before the effective filing date of the claimed invention by administering an effective amount of hyaluronan-nimesulide in appropriate nimesulide equivalents, and adjusting the treatment period to successfully treat a patient, to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to modify the dosage of a component of the pharmaceutical composition and the treatment regimen taught by Tchaparian with the dosage of hyaluronan-conjugate in nimesulide equivalents and the treatment period according to the teachings of ClinicalTrial because ClinicalTrial teaches that the part 1 of their study is to determine the safety and tolerability of three dose levels of CA102N as monotherapy and the safety, tolerability and preliminary recommended phase 2 dose (RP2D) of CA102N in combination with trifluridine/tipiracil (LONSURF®) in patients with locally advanced or metastatic solid tumors (Detailed Description). One of ordinary skill in the art would have a reasonable expectation of success because ClinicalTrial is a successfully completed first-in-human study with primary outcome measure of the study being the safety and tolerability of CA102N monotherapy and CA102N combined with trifluridine/tipiracil (LONSURF®) as determined according to the NCI-CTCAE version 5.0 (Study plan - Primary outcome measures).
Thus, instant claims 1 – 3, 5, and 7 – 9 are rejected by the combined teachings of Tchaparian and ClinicalTrial.
Response to Arguments
In Applicant’s arguments, see pg. 1 – 3, filed 02/10/2026, Applicant argues that claim 1 has been amended to incorporate limitations of original claims 6 and 12 which are not taught by Tchaparian, ClinicalTrial, Jian et al, Lee et al, Sochacka-Cwikla et al, and Tomaz et al whether considered individually or in any combination. Applicant’s arguments have been carefully considered, but are not persuasive. Due to the amendments to claim 1, the teachings of Jian et al, Lee et al, Sochacka-Cwikla et al, and Tomaz et al were not used in the new grounds of rejection presented above.
Applicant argues against the rejection of the original claims 1, 4, 6, and 10 – 12 under U.S.C. 103 as being unpatentable over Tchaprian as the formulations taught by Tchaparian are not the same as the instant formulations. This argument isn’t persuasive. As claim 1 is amended to incorporate the limitations from the original claims 4, 6, and 10 – 13, a new ground of rejection has been presented 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.
US 12,285,441 B2
Claims 1 – 3, 5, and 7 – 9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 12,285,441 in view of Eskouhie Tchaparian and Louis Lin, Cancer Res 2018;78(13 Suppl):Abstract nr 5811 (IDS 08/30/2025) and (First-in-human Study of CA102N Monotherapy and CA102N Combined With Trifluridine/Tipiracil (LONSURF) in Subjects With Advanced Solid Tumors, https://clinicaltrials.gov/study/NCT03616574, first started on 4/9/2019) (IDS 10/02/2024).
Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 of the ‘441 patent is drawn to a method for treating breast cancer comprising a step of administering to a subject in need thereof a therapeutically effective amount of a conjugate of a hyaluronic acid and an active compound, wherein the active compound is nimesulide.
The claims of the ‘441 patent differ from the instantly claimed invention in that the ‘441 patent lacks an additional effective amount of fluoropyrimidine, 5-FU to be administered along with a therapeutically effective amount of a conjugate of a hyaluronic acid and an active compound, wherein the active compound is nimesulide.
Tchaparian teaches that the combination of CA102N and 5-FU represents a promising potential therapeutic strategy in the treatment of colorectal cancer. It teaches that the combination therapy displayed a marked reduction in tumor growth and that the drug combination displayed a synergistic antitumoral effect in HT29 Xenograft mice models. It teaches the intravenous administration of CA102N with the dosage 200mg/kg administered twice a week (BIW)(i.v. 200mg/kg, BIW) & also with the dosage 400mg/kg administered once a week(QW). It also teaches the intravenous administration of 5-FU with the dosage 50mg/kg, once a week(i.v. 50mg/kg, QW). It teaches the treatment period as 21 days.
ClinicalTrial (Detailed description) teaches the first-in-human study of CA102N monotherapy and of CA102N combined with trifluridine/tipiracil(LONSURF®) in subjects with advanced or metastatic solid tumors. It also teaches the application of the combination therapy in subjects with metastatic colorectal cancer. It teaches the dosage of CA102N as 0.36, 0.54, and 0.72 mg/kg of nimesulide equivalents on days 1 and 15 of a 28-day cycle (Arms and Interventions) and LONSURF® dosage as 35 mg/m2/dose orally twice daily on days 1 through 5 and days 8 through 12 of each 28-day cycle.
It would have been obvious for one of ordinary skill in the art to modify the claim of the ‘441 patent with the teachings of Tchaparian and ClinicalTrial to do a co-administration of HA-nimesulide conjugate with a fluoropyrimidine, 5-FU to arrive at the instantly claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to modify the claims of the ‘441 patent by including an effective amount of a fluoropyrimidine because Tchaparian teaches that the drug combination displayed a synergistic antitumoral effect. One of ordinary skill in the art would have a reasonable expectation of success because of the teachings of Tchaparian and ClinicalTrial to extend the administration of the improved pharmaceutical composition to the treatment of a broad genus of solid and liquid tumors.
This is a nonstatutory double patenting rejection.
US 10,342,878 B2
Claims 1 – 3, 5, and 7 – 9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 2 of U.S. Patent No. 10,342,878 in view of Eskouhie Tchaparian and Louis Lin, Cancer Res 2018;78(13 Suppl):Abstract nr 5811 (IDS 08/30/2025) and (First-in-human Study of CA102N Monotherapy and CA102N Combined With Trifluridine/Tipiracil (LONSURF) in Subjects With Advanced Solid Tumors, https://clinicaltrials.gov/study/NCT03616574, first started on 4/9/2019) (IDS 10/02/2024).
Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1 and 2 of the ‘878 patent are drawn to a method for treatment of cancer comprising a step of administering a therapeutically effective amount of a compound consisting of a conjugate from a hyaluronic acid and an active compound, wherein the hyaluronic acid has an average molecular weight comprised in the range from 10 kDa to 2000 kDa. Nimesulide is a species recited in the genus of active compounds in the ‘878 patent and the method of treatment is directed to colon cancer or glioblastoma.
The claims of the ‘878 patent differ from the instantly claimed invention in that the ‘878 patent lacks an additional effective amount of fluoropyrimidine, 5-FU to be administered along with a therapeutically effective amount of a conjugate of a hyaluronic acid and an active compound, where nimesulide is a species of active compounds which is conjugated to the hyaluronic acid.
Tchaparian teaches that the combination of CA102N and 5-FU represents a promising potential therapeutic strategy in the treatment of colorectal cancer. It teaches that the combination therapy displayed a marked reduction in tumor growth and that the drug combination displayed a synergistic antitumoral effect in HT29 Xenograft mice models. It teaches the intravenous administration of CA102N with the dosage 200mg/kg administered twice a week (BIW)(i.v. 200mg/kg, BIW) & also with the dosage 400mg/kg administered once a week(QW). It also teaches the intravenous administration of 5-FU with the dosage 50mg/kg, once a week(i.v. 50mg/kg, QW). It teaches the treatment period as 21 days.
ClinicalTrial (Detailed description) teaches the first-in-human study of CA102N monotherapy and of CA102N combined with trifluridine/tipiracil(LONSURF®) in subjects with advanced or metastatic solid tumors. It also teaches the application of the combination therapy in subjects with metastatic colorectal cancer. It teaches the dosage of CA102N as 0.36, 0.54, and 0.72 mg/kg of nimesulide equivalents on days 1 and 15 of a 28-day cycle (Arms and Interventions) and LONSURF® dosage as 35 mg/m2/dose orally twice daily on days 1 through 5 and days 8 through 12 of each 28-day cycle.
It would have been obvious for one of ordinary skill in the art to modify the claims of the ‘878 patent with the teachings of Tchaparian and ClinicalTrial to do a co-administration of HA-nimesulide conjugate with a fluoropyrimidine, 5-FU to arrive at the instantly claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to modify the claims of the ‘878 patent by including an effective amount of a fluoropyrimidine because Tchaparian teaches that the drug combination displayed a synergistic antitumoral effect. One of ordinary skill in the art would have a reasonable expectation of success because of the teachings of Tchaparian and ClinicalTrial to extend the administration of the improved pharmaceutical composition to the treatment of a broad genus of solid and liquid tumors.
This is a nonstatutory double patenting rejection.
US 9,572,832 B2
Claims 1 – 3, 5, and 7 – 9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 5 of U.S. Patent No. 9,572,832 in view of Eskouhie Tchaparian and Louis Lin, Cancer Res 2018;78(13 Suppl):Abstract nr 5811 (IDS 08/30/2025) and (First-in-human Study of CA102N Monotherapy and CA102N Combined With Trifluridine/Tipiracil (LONSURF) in Subjects With Advanced Solid Tumors, https://clinicaltrials.gov/study/NCT03616574, first started on 4/9/2019) (IDS 10/02/2024).
Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1 and 5 of the ‘832 patent are drawn to a compound consisting of a conjugate from a hyaluronic acid and an active compound wherein nimesulide is a species of active compounds, and it is for use in the treatment of colon cancer, or glioblastoma.
The claims of the ‘832 patent differ from the instantly claimed invention in that the ‘832 patent lacks an additional effective amount of fluoropyrimidine, 5-FU to be administered along with a therapeutically effective amount of a conjugate of a hyaluronic acid and an active compound, where nimesulide is a species of active compounds which is conjugated to the hyaluronic acid.
Tchaparian teaches that the combination of CA102N and 5-FU represents a promising potential therapeutic strategy in the treatment of colorectal cancer. It teaches that the combination therapy displayed a marked reduction in tumor growth and that the drug combination displayed a synergistic antitumoral effect in HT29 Xenograft mice models. It teaches the intravenous administration of CA102N with the dosage 200mg/kg administered twice a week (BIW)(i.v. 200mg/kg, BIW) & also with the dosage 400mg/kg administered once a week(QW). It also teaches the intravenous administration of 5-FU with the dosage 50mg/kg, once a week(i.v. 50mg/kg, QW). It teaches the treatment period as 21 days.
ClinicalTrial (Detailed description) teaches the first-in-human study of CA102N monotherapy and of CA102N combined with trifluridine/tipiracil(LONSURF®) in subjects with advanced or metastatic solid tumors. It also teaches the application of the combination therapy in subjects with metastatic colorectal cancer. It teaches the dosage of CA102N as 0.36, 0.54, and 0.72 mg/kg of nimesulide equivalents on days 1 and 15 of a 28-day cycle (Arms and Interventions) and LONSURF® dosage as 35 mg/m2/dose orally twice daily on days 1 through 5 and days 8 through 12 of each 28-day cycle.
It would have been obvious for one of ordinary skill in the art to modify the claim of the ‘832 patent with the teachings of Tchaparian and ClinicalTrial to do a co-administration of HA-nimesulide conjugate with a fluoropyrimidine, 5-FU to arrive at the instantly claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to modify the claims of the ‘832 patent by including an effective amount of a fluoropyrimidine because Tchaparian teaches that the drug combination displayed a synergistic antitumoral effect. One of ordinary skill in the art would have a reasonable expectation of success because of the teachings of Tchaparian and ClinicalTrial to extend the administration of the improved pharmaceutical composition to the treatment of a broad genus of solid and liquid tumors.
This is a nonstatutory double patenting rejection.
US 11,643,431 B2
Claims 1 – 3, 5, and 7 – 9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1- 12 of U.S. Patent No. 11,643,431 in view of Eskouhie Tchaparian and Louis Lin, Cancer Res 2018;78(13 Suppl):Abstract nr 5811 (IDS 08/30/2025) and (First-in-human Study of CA102N Monotherapy and CA102N Combined With Trifluridine/Tipiracil (LONSURF) in Subjects With Advanced Solid Tumors, https://clinicaltrials.gov/study/NCT03616574, first started on 4/9/2019) (IDS 10/02/2024).
Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1 -12 of the ‘431 patent recite hyaluronan conjugate. The hyaluronan conjugate is a hyaluronic acid (HA)-nimesulide conjugate. The ‘431 patent claims the use of these compounds for treating pulmonary infection.
The claims of the ‘431 patent differ from the instantly claimed invention in that the compounds are not used to treat cancer and it lacks an additional effective amount of fluoropyrimidine, 5-FU to be administered along with a therapeutically effective amount of a hyaluronan-nimesulide conjugate.
Tchaparian teaches that the combination of CA102N and 5-FU represents a promising potential therapeutic strategy in the treatment of colorectal cancer. It teaches that the combination therapy displayed a marked reduction in tumor growth and that the drug combination displayed a synergistic antitumoral effect in HT29 Xenograft mice models. It teaches the intravenous administration of CA102N with the dosage 200mg/kg administered twice a week (BIW)(i.v. 200mg/kg, BIW) & also with the dosage 400mg/kg administered once a week(QW). It also teaches the intravenous administration of 5-FU with the dosage 50mg/kg, once a week(i.v. 50mg/kg, QW). It teaches the treatment period as 21 days.
ClinicalTrial (Detailed description) teaches the first-in-human study of CA102N monotherapy and of CA102N combined with trifluridine/tipiracil(LONSURF®) in subjects with advanced or metastatic solid tumors. It also teaches the application of the combination therapy in subjects with metastatic colorectal cancer. It teaches the dosage of CA102N as 0.36, 0.54, and 0.72 mg/kg of nimesulide equivalents on days 1 and 15 of a 28-day cycle (Arms and Interventions) and LONSURF® dosage as 35 mg/m2/dose orally twice daily on days 1 through 5 and days 8 through 12 of each 28-day cycle.
It would have been obvious for one of ordinary skill in the art to modify the claim of the ‘431 patent with the teachings of Tchaparian and ClinicalTrial to do a co-administration of HA-nimesulide conjugate with a fluoropyrimidine to treat cancer to arrive at the instantly claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to modify the claims of the ‘431 patent by including an effective amount of a fluoropyrimidine, 5-FU because Tchaparian teaches that the drug combination displayed a synergistic antitumoral effect. One of ordinary skill in the art would have a reasonable expectation of success because of the teachings of Tchaparian and ClinicalTrial to extend the administration of the improved pharmaceutical composition to the treatment of a broad genus of solid and liquid tumors.
This is a nonstatutory double patenting rejection.
US 12,281,133 B2
Claims 1 – 3, 5, and 7 – 9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1- 4 of U.S. Patent No. 12,281,133 in view of Eskouhie Tchaparian and Louis Lin, Cancer Res 2018;78(13 Suppl):Abstract nr 5811 (IDS 08/30/2025) and (First-in-human Study of CA102N Monotherapy and CA102N Combined With Trifluridine/Tipiracil (LONSURF) in Subjects With Advanced Solid Tumors, https://clinicaltrials.gov/study/NCT03616574, first started on 4/9/2019) (IDS 10/02/2024).
Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-4 of the ‘133 patent recite the hyaluronan-nimesulide conjugates having one or two disaccharide units.
The ‘133 patent differs from the instantly claimed invention in that the administration of the compounds to treat cancer is not claimed and it lacks an additional effective amount of fluoropyrimidine, 5-FU to be administered along with a therapeutically effective amount of a hyaluronan-nimesulide conjugate.
Tchaparian teaches that the combination of CA102N and 5-FU represents a promising potential therapeutic strategy in the treatment of colorectal cancer. It teaches that the combination therapy displayed a marked reduction in tumor growth and that the drug combination displayed a synergistic antitumoral effect in HT29 Xenograft mice models. It teaches the intravenous administration of CA102N with the dosage 200mg/kg administered twice a week (BIW)(i.v. 200mg/kg, BIW) & also with the dosage 400mg/kg administered once a week(QW). It also teaches the intravenous administration of 5-FU with the dosage 50mg/kg, once a week(i.v. 50mg/kg, QW). It teaches the treatment period as 21 days.
ClinicalTrial (Detailed description) teaches the first-in-human study of CA102N monotherapy and of CA102N combined with trifluridine/tipiracil(LONSURF®) in subjects with advanced or metastatic solid tumors. It also teaches the application of the combination therapy in subjects with metastatic colorectal cancer. It teaches the dosage of CA102N as 0.36, 0.54, and 0.72 mg/kg of nimesulide equivalents on days 1 and 15 of a 28-day cycle (Arms and Interventions) and LONSURF® dosage as 35 mg/m2/dose orally twice daily on days 1 through 5 and days 8 through 12 of each 28-day cycle.
It would have been obvious for one of ordinary skill in the art to modify the claim of the ‘133 patent with the teachings of Tchaparian and ClinicalTrial to do a co-administration of HA-nimesulide conjugate with a fluoropyrimidine to treat cancer to arrive at the instantly claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to modify the claims of the ‘133 patent by including an effective amount of a fluoropyrimidine, 5-FU because Tchaparian teaches that the drug combination displayed a synergistic antitumoral effect. One of ordinary skill in the art would have a reasonable expectation of success because of the teachings of Tchaparian and ClinicalTrial to extend the administration of the improved pharmaceutical composition to the treatment of a broad genus of solid and liquid tumors.
This is a nonstatutory double patenting rejection.
Claims 1 – 3, 5, and 7 – 9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 4 of Application No. 17/843,534 in view of Eskouhie Tchaparian and Louis Lin, Cancer Res 2018;78(13 Suppl):Abstract nr 5811 (IDS 08/30/2025) and (First-in-human Study of CA102N Monotherapy and CA102N Combined With Trifluridine/Tipiracil (LONSURF) in Subjects With Advanced Solid Tumors, https://clinicaltrials.gov/study/NCT03616574, first started on 4/9/2019) (IDS 10/02/2024).
Claims 1 – 3, 5, and 7 – 9 of this application are patentably indistinct from claims 1 – 4 of co-pending Application No. 17/843,534.
Claim 1 of the co-pending application ‘534 recites a method for treating cancer comprising of a step of administering an effective amount of a hyaluronan conjugate wherein the conjugate consists of one to four disaccharide units of D-glucuronic acid and N-acetylglucosamine, and one or more hydrogenated nimesulide, and the cancer is breast cancer, lung cancer, or colorectal cancer. Claims 2- 4 of co-pending application ‘534 are drawn to different structures of the HA-Nim conjugate.
The claim 1 of the application ‘534 differs from the instantly claimed invention in that the ‘534 application lacks an additional effective amount of fluoropyrimidine, 5-FU to be administered along with a therapeutically effective amount of a conjugate of a hyaluronic acid.
As both sets of claims recite a method of treatment of breast tumor, colorectal tumor or lung tumor by the administration of HA-nimesulide conjugate, even though they are not exactly matching, they are overlapping in scope. Thus rendering one set of claims to be unpatentable.
Tchaparian teaches that the combination of CA102N and 5-FU represents a promising potential therapeutic strategy in the treatment of colorectal cancer. It teaches that the combination therapy displayed a marked reduction in tumor growth and that the drug combination displayed a synergistic antitumoral effect in HT29 Xenograft mice models. It teaches the intravenous administration of CA102N with the dosage 200mg/kg administered twice a week (BIW)(i.v. 200mg/kg, BIW) & also with the dosage 400mg/kg administered once a week(QW). It also teaches the intravenous administration of 5-FU with the dosage 50mg/kg, once a week(i.v. 50mg/kg, QW). It teaches the treatment period as 21 days.
ClinicalTrial (Detailed description) teaches the first-in-human study of CA102N monotherapy and of CA102N combined with trifluridine/tipiracil(LONSURF®) in subjects with advanced or metastatic solid tumors. It also teaches the application of the combination therapy in subjects with metastatic colorectal cancer. It teaches the dosage of CA102N as 0.36, 0.54, and 0.72 mg/kg of nimesulide equivalents on days 1 and 15 of a 28-day cycle (Arms and Interventions) and LONSURF® dosage as 35 mg/m2/dose orally twice daily on days 1 through 5 and days 8 through 12 of each 28-day cycle.
The combined teachings of Tchaparian and ClinicalTrail certainly render obvious the co-administration of an effective amount of HA-nimesulide conjugate and an effective amount of a fluoropyrimidine, 5-FU for the treatment of solid or liquid tumors.
This is a provisional nonstatutory double patenting rejection.
Claims 1 – 3, 5, and 7 – 9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 9, and 10 of Application No. 18/624,744 in view of Eskouhie Tchaparian and Louis Lin, Cancer Res 2018;78(13 Suppl):Abstract nr 5811 (IDS 08/30/2025) and (First-in-human Study of CA102N Monotherapy and CA102N Combined With Trifluridine/Tipiracil (LONSURF) in Subjects With Advanced Solid Tumors, https://clinicaltrials.gov/study/NCT03616574, first started on 4/9/2019) (IDS 10/02/2024).
Claims 1 – 3, 5, and 7 – 9 of this application are patentably indistinct from claims 1, 9 and 10 of co-pending Application No. 18/624,744.
Claim 1 of the co-pending application ‘744 recites a method for treating cancer comprising of a step of administering an effective amount of a conjugate of a hyaluronic acid and an active compound including nimesulide, and the cancer is pancreatic cancer. Nimesulide is a species of a genus of active compounds recited in the claim. Claims 9 and 10 of the co-pending application ‘744 recite how nimesulide is conjugated with HA to form HA-nimesulide conjugate.
The claim 1 of the application ‘744 differs from the instantly claimed invention in that the ‘744 application lacks an additional effective amount of fluoropyrimidine, 5-FU to be administered along with a therapeutically effective amount of a conjugate of a hyaluronic acid.
As both sets of claims recite a method of treatment of pancreatic tumor by the administration of HA-nimesulide conjugate, even though they are not exactly matching, they are overlapping in scope. Thus rendering one set of claims to be unpatentable.
Tchaparian teaches that the combination of CA102N and 5-FU represents a promising potential therapeutic strategy in the treatment of colorectal cancer. It teaches that the combination therapy displayed a marked reduction in tumor growth and that the drug combination displayed a synergistic antitumoral effect in HT29 Xenograft mice models. It teaches the intravenous administration of CA102N with the dosage 200mg/kg administered twice a week (BIW)(i.v. 200mg/kg, BIW) & also with the dosage 400mg/kg administered once a week(QW). It also teaches the intravenous administration of 5-FU with the dosage 50mg/kg, once a week(i.v. 50mg/kg, QW). It teaches the treatment period as 21 days.
ClinicalTrial (Detailed description) teaches the first-in-human study of CA102N monotherapy and of CA102N combined with trifluridine/tipiracil(LONSURF®) in subjects with advanced or metastatic solid tumors. It also teaches the application of the combination therapy in subjects with metastatic colorectal cancer. It teaches the dosage of CA102N as 0.36, 0.54, and 0.72 mg/kg of nimesulide equivalents on days 1 and 15 of a 28-day cycle (Arms and Interventions) and LONSURF® dosage as 35 mg/m2/dose orally twice daily on days 1 through 5 and days 8 through 12 of each 28-day cycle.
The combined teachings of Tchaparian and ClinicalTrail certainly render obvious the co-administration of an effective amount of HA-nimesulide conjugate and an effective amount of a fluoropyrimidine, 5-FU for the treatment of solid or liquid tumors.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant did not submit any arguments over the double-patenting rejections. MPEP states “A complete response to a nonstatutory double patenting (NSDP) rejection is either a reply by applicant showing that the claims subject to the rejection are patentably distinct from the reference claims, or the filing of a terminal disclaimer in accordance with 37 CFR 1.321 in the pending application(s) with a reply to the Office action (see MPEP § 1490 for a discussion of terminal disclaimers). Such a response is required even when the nonstatutory double patenting rejection is provisional.”
The rejection is found to be proper, and is therefore maintained.
Conclusion
Claims 1 – 3, 5, and 7 – 9 are rejected. No claims are allowed.
Applicant’s amendment necessitated new ground(s) of rejection presented in this Office action. Accordingly, 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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/JANAKI ANANTH MAHADEVAN/Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693