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 .
EXAMINER’S AMENDMENT
An examiner’s amendment to the record appears below. Should the changes and/or additions be unacceptable to applicant, an amendment may be filed as provided by 37 CFR 1.312. To ensure consideration of such an amendment, it MUST be submitted no later than the payment of the issue fee.
Authorization for this examiner’s amendment was given in a telephone call with Applicant’s representative, Attorney James H. Walters on 07/22/2026.
The examiner’s amendments are presented on the next page and summarized below:
Claim 1 is amended.
The following examiner’s amendment applies to the claim set filed on 05/18/2026:
1. (Currently Amended) A method for treating cancer in a subject that has been diagnosed with the cancer, comprising the step of administering to the subject an effective amount of a hyaluronan conjugate, wherein (1) the hyaluronan conjugate consists of one to
Status of Claims/Application
Applicant’s amendment and remarks, dated 05/18/2026, is acknowledged.
Claims 1, and 7 have been amended. Claim 4 has been canceled. No new claims have been added.
In view of the examiner’s amendment, claims 1 – 3, 5, and 7 are currently pending and are examined on the merits herein.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e)
or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. The instant application
claims domestic benefit of the provisional application, Application No. 63/212,297, filed
on 6/18/2021.
Withdrawn Objections and Rejections
The objection regarding the clarity of structures in the claims 2, 3 and 4 are withdrawn as the images are sharper in claims 2 and 3. As claim 4 is canceled, the objection is moot.
The rejection of claims 1 – 5, and 7 under 35 USC 112(a) is withdrawn with the amendment to claim 1 that recites A method for treating cancer in a subject “that has been diagnosed with the cancer” as it no longer encompasses prophylactic or preventative treatment.
The rejection of claims 1 – 5, and 7 under 35 USC 103 as being unpatentable over US 2017/0151336 in view of Tavianatou and Han is withdrawn. As claim 1 is amended, the rejection is overcome as indicated in the response to the arguments below.
Response to Arguments
Applicant argues that the instant claims are directed to a structurally and functionally distinct class of hyaluronan conjugates, namely ultra-short HA conjugates consisting of only one or two disaccharide units covalently linked to hydrogenated nimesulide, while US’336 teaches conjugates with high molecular weight HA (10 kDa to 2000 kDa), with its lowest molecular weight corresponding to at least 26 disaccharide units without suggesting or teaching that ultra-short HA fragments would be suitable for drug conjugation with intended biological effects.
Applicant argues that Tavianatou teaches that HA biological function is highly dependent on molecular size, and that effective receptor interactions require at least 6 saccharide units, with increasing chain length leading to more stable and multivalent interactions, and provides no motivation to reduce HA to one or two disaccharide units.
Applicant argues that Han teaches that very short fragment of free HA oligosaccharides (DP2 and DP3) exhibit weak or negligible effects, with DP4 being the minimum fragment showing activity.
Applicant argues that both Tavianatou and Han teach free HA oligosaccharides, and not drug conjugates of the instant application.
The applicant’s arguments are persuasive on account of the amendment to claim 1, to recite a hyaluronan conjugate consisting of one to two disaccharide units of D-glucuronic acid and N-acetylglucosamine, and one or two hydrogenated nimesulide, each covalently linked to the D-glucuronic acid of one of the disaccharide units.
Applicant also argues that they demonstrate that their invention exhibits unexpected and non-predictable properties which strongly support non-obviousness. NIM-Tetra exhibits significantly greater cytotoxicity in MDA-MB-231 breast cancer cells than DP4 alone (150 µM compared to 100 mM). This argument is persuasive.
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 11,643,431 B2
Claims 1- 3, 5, and 7 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 US 2017/0151336 A1 (PTO-892, 02/18/2016).
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 the same compounds
and structures of the instantly claimed invention. 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.
US’336 teaches a method of treating cancer by administering HA conjugated with
an active compound. Nimesulide is a species of the claimed active compounds. US’336 teaches that the antitumor efficacy of Nimesulide conjugated with HA when compared with Nimesulide alone showed significantly improved cytotoxicity effect and tumor suppression efficacy.
It would have been obvious for one of ordinary skill in the art to modify the
claims of the ‘431 patent with the teachings of US’336 to administer the compounds of
the ‘431 patent to a patient suffering from cancer. It would have been prima facie
obvious for one of ordinary skill in the art to modify the claims of the ‘431 patent to find
a new effective use for the compounds because US’336 teaches that Nimesulide conjugated with HA showed improved cytotoxicity and tumor suppression efficacy, thus
arriving at the instantly claimed invention.
This is a nonstatutory double patenting rejection.
US 12,281,133 B2
Claims 1- 3, 5, and 7 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 US 2017/0151336 A1 (PTO-892, 02/18/2016).
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 same compounds and
structures of the instantly claimed invention.
The ‘133 patent differs from the instantly claimed invention in that the
administration of the compounds to treat cancer is not claimed.
US’336 teaches a method of treating cancer by administering HA conjugated with
an active compound. Nimesulide is a species of the claimed active compounds. US’336 teaches that the antitumor efficacy of Nimesulide conjugated with HA when compared with Nimesulide alone showed significantly improved cytotoxicity effect and tumor suppression efficacy.
It would have been obvious for one of ordinary skill in the art to modify the
claims of the ‘133 patent with the teachings of US’336 to administer the compounds of the ‘133 patent to a patient suffering from cancer. It would have been prima facie
obvious for one of ordinary skill in the art to modify the claims of the ‘133 patent to find
an effective use for the compounds because US’336 teaches that Nimesulide conjugated
with HA showed improved cytotoxicity and tumor suppression efficacy, thus arriving at
the instantly claimed invention.
This is a nonstatutory double patenting rejection.
Claims 1 – 3, 5, and 7 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 3, 5, and 7 – 9 of Application No. 18/365,528.
Claims 1 – 3, 5, and 7 of this application are patentably indistinct from claims 1 – 3, 5, and 7 – 9 of co-pending Application No. 18/365,528.
Claims 1 and 2 of the co-pending application recite a method for the curative or palliative treatment of a locally advanced or metastatic solid or liquid tumor, comprising administering to a patient in need thereof an effective amount of a hyaluronan-nimesulide conjugate and an effective amount of fluoropyrimidine, wherein the hyaluronan-nimesulide conjugate is administered to the patient intravenously at 5 to 150 mg/kg/dose of hyaluronan-nimesulide conjugate; the fluoropyrimidine is 5-fluorouracil and is administered to the patient intravenously once weekly at 1 to 30 mg/kg/dose, wherein the solid tumor is a pancreatic tumor, colorectal tumor, liver tumor, melanoma, lung tumor, breast tumor, ovarian tumor, head or neck tumor, stomach tumor, prostate tumor, esophageal tumor, cervical or vaginal tumor, or brain tumor.
The claims 1 and 2 of the ‘528 application differ from the instantly claimed
invention in that the ‘528 application includes an additional effective amount of
fluoropyrimidine 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.
This is a 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.”
Applicant was contacted on 07/27/2026 as a follow-up to the telephone conversation on 07/22/2026 to request a TD. However, they declined, and asked for an action. The rejection is found to be proper, and is therefore maintained.
Conclusion
Claims 1 – 3, 5, and 7 are rejected. No claims 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 JANAKI ANANTH MAHADEVAN whose telephone number is (571)272-0230. The examiner can normally be reached Monday-Friday 8-5PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Scarlett Goon can be reached at 5712705241. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/J.A.M./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693
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