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 .
DETAILED ACTION
Election of Species and Status of the Claims
Applicant’s election without traverse of ‘mebendazole’ as the single specific microtubule inhibitor and ‘glioblastoma’ as the single specific tumor or cancer in the response filed on January 9th 2026 is acknowledged. Claims 1, 3-5, 8-9, and 12-19 are pending and are examined on their merits.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The Information Disclosure Statement filed on September 26th 2024 is in compliance with the provisions of 37 CFR 1.97 and has been considered in full. A signed copy of references cited from the IDS is included with this Office Action.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2 and 15 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 3 is indefinite for reciting a composition “for simultaneous, separate, or sequential use,” because one of ordinary skill in the art could not reasonably determine how the phrase further limits the composition of claim 1. Specifically, the use of a composition is not patently distinct from the composition itself. Thereby, it is unclear how a composition “for use…” differs from the composition itself.
Claim 15 is indefinite for the phrase “and severe related tumours,” because one of ordinary skill could not reasonably determine the metes and bounds of claim 15 from the phrase. Specifically, the term is relative in nature, is not defined by the specification, but only briefly mentioned (specification, pg. 11), and it is unclear what tumors would be classified as “severe tumours related to glioblastoma.”
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 3, 4, and 17-19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chen (Chen et al., Increased spinal cord Na⁺-K⁺-2Cl⁻ cotransporter-1 (NKCC1) activity contributes to impairment of synaptic inhibition in paclitaxel-induced neuropathic pain. J Biol Chem. 2014 Nov 7;289(45):31111-20).
Claims 1, 3, and 4 are directed towards a composition comprising bumetanide and a microtubule inhibitor, wherein the microtubule inhibitor is selected from a group that includes taxanes such as paclitaxel, and the two compounds are administered at the same time or separately.
Chen teaches the administration of bumetanide after paclitaxel, a common chemotherapeutic drug, reduces neuropathic pain resulting from the paclitaxel administration (Chen, pg. 31117). Chen thereby anticipates claims 1, 3, and 4.
Claims 17 and 18 are directed towards the treatment or prevention of a tumor or cancer in a subject in need thereof, via administration of bumetanide and a microtubule inhibitor. It is noted that the prevention of a tumor or cancer necessarily requires that the subject in question does not have said tumor or cancer. Therefore, as Chen teaches the administration of bumetanide and paclitaxel (Chen, pg. 31117), Chen shares the patient population of claims 17 and 18 (subjects with or without the described cancer), and Chen anticipates claims 17 and 18.
Claim 19 is directed towards the method of claim 17 wherein the method further comprises chemotherapy. as Chen teaches the administration of bumetanide and paclitaxel (Chen, pg. 31117), and paclitaxel is a common therapeutic drug (Chen, Abstract), Chen anticipates claim 19.
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.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Chen.
Claim 9 requires that, in the composition of claim 1, at least one pharmaceutically acceptable carrier is present. Chen does not explicitly teach pharmaceutical carriers. Chen, however, does teach that both drugs are administered via injection (Chen, pg. 31112; Chen, pg. 31115). As pharmaceutical injections are well-known in the art to be administered in aqueous solutions, one of ordinary skill in the art would reasonably expect the solutions injected by Chen to include at least water in addition to the administered drugs. Claim 9 is thereby prima facie obvious.
Claims 5, 8, and 12-16 are rejected under 35 U.S.C. 103 as being unpatentable over Haas (Haas et al., Inhibition of the Sodium-Potassium-Chloride Cotransporter Isoform-1 Reduces Glioma Invasion, Cancer Res (2010) 70 (13): 5597–5606) in view of Chai (Chai et al., Albendazole and Mebendazole as Anti-Parasitic and Anti-Cancer Agents: an Update. Korean J Parasitol. 2021 Jun;59(3):189-225).
Claims 5, 8, and 12-15 are directed towards the treatment of glioblastoma via administration of a combination of bumetanide and mebendazole. Both drugs have been demonstrated in the art to be useful in the treatment of glioblastoma. See Haas, who teaches that bumetanide administration reduces glioma migration:
“Here, we show that the Sodium-Potassium-Chloride Cotransporter Isoform-1 (NKCC1) provides the major pathway for Cl− accumulation in glioma cells. NKCC1 localizes to the leading edge of invading process es, and pharmacologic inhibition using the loop diuretic bumetanide inhibits in vitro Transwell migration by 25% to 50%. Short hairpin RNA knockdowns of NKCC1 yielded a similar inhibition and a loss of bumetanide sensitive cell volume regulation. A loss of NKCC1 function did not affect cell motility in two-dimensional assays lacking spatial constraints but manifested only when cells had to undergo volume changes during migration. Intracranial implantation of human gliomas into severe combined immunodeficient mice showed a marked reduction in cell invasion when NKCC1 function was disrupted genetically or by twice daily injection of the Food and Drug Administration–approved NKCC1 inhibitor Bumex. These data support the consideration of Bumex as adjuvant therapy for patients with high-grade gliomas.”
[Haas, Abstract]
Chai teaches that the anthelmintic, mebendazole, is effective in the treatment of glioblastoma (Chai, pg. 208). As both drugs are known in the art to treat glioblastoma, one of ordinary skill in the art would have a reasonable expectation of success in treating glioblastoma with the combination of bumetanide and mebendazole. See MPEP § 2144.06(I):
"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious); and In re Couvaras, 70 F.4th 1374, 1378-79, 2023 USPQ2d 697 (Fed. Cir. 2023) (That the two claimed types of active agents, GABA-a agonists and ARBs, were known to be useful for the same purpose—alleviating hypertension—alone can serve as a motivation to combine).
Thereby, claims 5, 8, and 12-15 are prima facie obvious.
Claim 19 requires that, in the method of claim 17, the method further comprises any of chemotherapy, radiotherapy, or chemoradiotherapy. As chemotherapy is the treatment of cancer/killing of cancer cells via administration of pharmaceuticals, it is described by the combination of Haas and Chai (above), and claim 19 is prima facie obvious.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Anthony Seitz whose telephone number is (703)756-4657. The examiner can normally be reached 7:30 AM ET - 5:00 PM ET M-F.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Lundgren can be reached at (571)272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/A.J.S./Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
Prosecution Insights