DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Application
This Office Action is in response to Applicant's arguments filed on October 21, 2025. Claim(s) 1, 2, 4, 6-8, 10, and 11 are pending and examined herein.
Response to Arguments
In view of Applicant’s amendments, the following rejections are hereby withdrawn:
Claims 1-6 and 8 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Smith (US 2015/0045401) as evidenced by Dubinett (WO 2016/073759).
Claims 7 and 10-13 are rejected under 35 U.S.C. 103 as being unpatentable over Smith (US 2015/0045401) in view of Dubinett (WO 2016/073759) as applied to claims 1-6 and 8 in the 102(a)(1) rejection above.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Smith (US 2015/0045401) in view of Dubinett (WO 2016/073759) as applied to claims 1-6 and 8 in the 102(a)(1) rejection above.
Claims 7 and 10-13 are rejected under 35 U.S.C. 103 as being unpatentable over Smith (US 2015/0045401) in view of Dubinett (WO 2016/073759) as applied to claims 1-6 and 8 in the 102(a)(1) rejection above.
Applicant’s decision to hold the nonstatutory double patenting rejection of claims 1-13 as being unpatentable over claims 1-19 of US 11,400,155 is hereby maintained.
Applicant’s arguments with respect to the 35 U.S.C. 112, first paragraph rejection of claims 1-13 as being enabling for a method of treating cancers selected from melanoma and glioblastoma, but does not reasonably provide enablement for the treatment of any cancer have been fully considered.
Applicant argues:
The present application discloses and claims the compound (troriluzole) known as a glutamate modulator which treat various types of cancer using a common mechanism of action.
Term "cancer" is well-known to a person of ordinary skill in the art. Cancer is a disease in which some of the body's cells, called cancer cells, grow uncontrollably and spread to other parts of the body. Compared to normal cells, cancer cells are characterized by the rapid proliferation, followed by a highly active metabolism. Glutamate is a major bioenergy substrate for cancer cell growth. It is crucial in cancer and rapidly proliferating cells by directly participating in the abovementioned metabolic processes. All cancer cells need more glutamate than normal tissues for energy supply, anti-oxidation activity, and biomass production. Glutamate influences tumor progression by acting on its receptors as ample studies have demonstrated the expression of glutamate receptors in a broad range of cancer cells.
Genes related to metabolic chains in many cancers are somehow mutated, which makes cancer cells more glutamate dependent. Increasing evidence has shown involvement of glutamate signaling, guided through glutamate receptors, in human malignancy. Dysregulation of glutamate transporters, such as excitatory amino acid transporter and cystine/glutamate antiporter system, also generates excessive extracellular glutamate, which in turn, activates glutamate receptors on cancer cells of various types and results in malignant growth.
The dependence of cancer cells on glutamate metabolism has made it an attractive anticancer therapeutic target. The present application identifies a compound that modulates the uptake of glutamate by cancerous cells thereby slowing down their proliferation and metabolism. Because glutamate uptake is common to cancer cells, a person of ordinary skill in the art would have no issue understanding that the claimed riluzole prodrug is useful to treat cancers of various types, not necessarily limited to glioblastoma and melanoma, and would be able to make and use the claimed invention without undue experimentation.
Examiner respectfully notes that applicant’s arguments are not commensurate in scope of the claimed invention. Applicant has demonstrated the effectiveness of the claimed composition as a method of modulating glutamate wherein a disease treatable by such modulation is cancer. Applicant, however, has not demonstrated that all cancers embraced by the umbrella term “cancer” benefit from such a therapeutic regimen.
Any rejection from the previous Office action not set forth on record below is hereby withdrawn.
The maintained/modified rejections are made in the Final Office action below as necessitated by amendment.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 2, 4, 6-8, 10, and 11 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for a method of treating cancers selected from melanoma and glioblastoma, does not reasonably provide enablement for the treatment of any cancer. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims. The specification does not provide sufficient information that all cancers are treatable by riluzole and a checkpoint inhibitor as described in the methods claimed.
The determination that “undue experimentation” would have been needed to make and use the claimed invention is not a single, simple factual determination. Rather, it is a conclusion reached by weighing all the above noted factual considerations. In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue”. These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The breadth of the claims
There are hundreds of types of cancers and tumors which can occur in any part of the body as set forth on record in previous Office action (12/27/24). Thus, “cancer” is an umbrella term rendering the claims extremely broad.
The nature of the invention
The nature of the invention is the treatment of any cancer through the use of the claimed compound. Currently, there are no known agents that treat all types of cancers inclusively.
The level of predictability in the art
D'Errico (Clinical and Translational Medicine, 2017) teaches immunotherapy is still far from becoming the perfect magic bullet to fight cancer, largely due to the facts that immunotherapy is not effective in all patients nor in all cancer types (Abstract).
Zugazagoitia (Clinical Therapeutics, 2016) teaches targeting a single hallmark or pathway with a single drug (“magic bullet”) will not likely lead to cancer cure (page 1564, Conclusion).
Thus, the treatment of cancer generally is highly unpredictable. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
The amount of direction provided by the inventor
The specification does not provide guidance for the treatment of the scope of disorders embraced by umbrella term cancer as recited by the instant claims. In the instant application, the effectiveness of the claimed composition is employed to see the modified survival rate in a glioblastoma animal model (Figure 1, page 16, Tumor Model).
The existence of working examples
There is not seen in the disclosure, sufficient evidence to support Applicant’s claims of treating these disorders. A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 27 USPQ2d 1510 (CAFC). The disclosure does not demonstrate sufficient evidence to support the applicant's claim to the treatment and methods in inhibition. There are not sufficient working examples or data from references of the prior art to provide a nexus between those examples and a method of treating these disorders with the claimed compound.
In the instant application, the effectiveness of the claimed composition is employed to see the modified survival rate in a glioblastoma animal model (Figure 1, page 16, Tumor Model).
The level of one of ordinary skill
The level of skill is that of one with a doctoral understanding of cancer, which embraces the multitude of diseases recited above. Applicant’s data is not convincing as to the use of pharmaceutical compositions comprising the recited compound feasible without undue, unpredictable experimentation.
The quantity of experimentation
A great deal of experimentation is required. In order for there to be a method of treating these disorders generally, as claimed by the applicant, it would be necessary to show that a vast range of different types of cancers as discussed above are treatable by said regimen. Furthermore, direction, in the form of examples, must be shown to determine what an effective dose may be. The references submitted do not demonstrate this. Therefore, one of ordinary skill in the art would require a significant amount of experimentation in order to determine the effective dosage to treat the multitudes of cancer types with the claimed compound individually or in combination with other therapeutic agents.
Genentech, 108 F.3d at 1366 states that "a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion" and "[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable." Therefore, a method for treating cancer, generally, by administering riluzole and a checkpoint inhibitor of the claims is not considered to be enabled by the instant specification.
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 claims at issue 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); and 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 2, 4, 6-8, 10, and 11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of US 11,400,155. Although the claims at issue are not identical, they are not patentably distinct from each other. The patented claims are drawn to a method of treating cancer by administering a combination therapy to a patient in need thereof comprising of an effective amount of a riluzole prodrug having formula as recited in claim 1, and an inhibitor of a checkpoint receptor selected from PD-1 and PD-L1, wherein the cancer is bladder cancer, breast cancer, colorectal cancer, gastrointestinal cancer, glioblastoma, lymphoma, melanoma, non-small cell lung cancer, ovarian cancer, prostate cancer, renal cell carcinoma, solid malignancy, and squamous cell carcinoma of head and neck. The instant claims are drawn to a method of treating cancer by administering a combination therapy to a patient in need thereof comprising of an effective amount of riluzole and a checkpoint inhibitor. The instant claims embrace the patented claims. Thus, the instant claims are unpatentable over the patented claims.
Conclusion
Claims 1, 2, 4, 6-8, 10, and 11 are not 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 extension fee 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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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sahar Javanmard whose telephone number is (571)270-3280. The examiner can normally be reached on Monday-Friday, 9:00-5:00 EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Alstrum-Acevedo can be reached on 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
/SAHAR JAVANMARD/Primary Examiner, Art Unit 1622