DETAILED ACTION
This office action is in response to applicant’s filing dated January 2, 2026.
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 Claims
Claims 5-24 and 29 are pending in the instant application. Acknowledgement is made of Applicant's amendments filed January 2, 2026. Acknowledgement is made of Applicant's amendment of claims 5, 17, and 18; and addition of new claim 29. Claims 1-4 and 25-28 were previously canceled.
Claims 5-24 and 29 are presently under examination.
Priority
The present application is a 371 of PCT/JP2021/033855 filed on September 15, 2021, which claims benefit of US Provisional Application No. 63/078,844 filed on September 15, 2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on October 13, 2025 and November 14, 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Withdrawn Objections and/or Rejections
Specification
The objection to the disclosure has been rendered moot in view of the amendment to the specification. Thus, the objection has been maintained.
Claim Rejections - 35 USC § 112(b)
Indefinite
The rejection of claim 17 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 has been rendered moot in view of the amendment to claim 17. Thus, the rejection has been withdrawn.
New Objections and/or Rejections
Necessitated by Claim Amendment
Claim Rejections - 35 USC § 112(a)
Scope of Enablement
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—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 or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 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 5-18 and 29 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating leukemia comprising administering the claimed compound, does not reasonably provide enablement for preventing leukemia. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. This is a scope of enablement rejection.
To be enabling, the specification of the patent application must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fd. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996). As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is "undue", not "experimentation".
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors:
1- the quantity of experimentation necessary,
2- the amount of direction or guidance provided,
3- the presence or absence of working examples,
4- the nature of the invention,
5- the state of the prior art,
6- the relative skill of those in the art,
7- the predictability of the art, and
8- the breadth of the claims
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
1. The nature of the invention, state and predictability of the art, and relative skill of those in the art
The invention relates to a method of preventing and/or treating leukemia in a patient in need thereof comprising administering an effective amount of comprising administering 5-chloro-2-(N-((1S,2R)-2-(6-fluoro-2,3-dimethylphenyl)-1-(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)propyl)sulfamoyl)benzamide.
The relative skill of those in the art is high, generally that of an M.D. or Ph.D. The artisan using Applicant’s invention would generally be a physician with a M.D. degree and several years of experience.
The factor is outweighed, however, by the unpredictable nature of the art. It is well established that “the scope of enablement varies with the degree of unpredictability of the factors involved” and physiological activity is considered to be an unpredictable factor. See In re Fisher, 166 USPQ 18, at 24 (In cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved); Nationwide Chemical Corporation, et. al. v. Wright, et. al., 192 USPQ 95 (one skilled in chemical and biological arts cannot always reasonably predict how different chemical compounds and elements might behave under varying circumstances); Ex parte Sudilovsky 21 USPQ2d 1702 (Applicant’s invention concerns pharmaceutical activity. Because there is no evidence of record of analogous activity for similar compounds, the art is relatively unpredictable); In re Wright 27 USPQ2d 1510 (the physiological activity of RNA viruses was sufficiently unpredictable that success in developing specific avian vaccine was uncertain). As illustrative of the state of the art of preventing leukemia, the examiner cites Whitehead et al (Curr Probl Pediatr Adolesc Health Care 2016; 46:317-352); Mejia-Arangure et al. (Frontiers in public health, 2021; 9:700739); and Emory Winship Cancer Institute (https://winshipcancer.emory.edu/cancer-types-and-treatments/leukemia/prevention.php, obtained from the internet March 18, 2026).
Whitehead teaches leukemia is the most common cancer in children; approximately 3800 children are diagnosed annually with acute lymphoblastic leukemia (ALL) or acute myeloblastic leukemia (AML) in the United States (U.S.) (page 317, left). Whitehead teaches there is a large and growing body of literature that demonstrates the role of environmental agents in determining the risk for childhood leukemias; this is in contrast to other pediatric cancers that are more rare and for which there have been far fewer environmental epidemiologic studies conducted (page 340, right, last bridge paragraph). Whitehead teaches despite the fact that many studies have identified modifiable risk factors (increased or decreased risk) for childhood leukemia we are aware of no current prevention program that specifically addresses childhood leukemia, anywhere in the world (page 341, left). Whitehead teaches at this time, despite steadily accumulating evidence that environmental exposures increase the risk of childhood leukemia, authoritative bodies, including the International Agency for Research on Cancer (IARC), consider only radiation and parents' active smoking as “causative” factors in the development of childhood leukemia (page 341, right, last paragraph). Whitehead further teaches primary prevention of cancer includes reducing exposures to risk factors or changing the underlying conditions which result in disease; while the CDC has been exploring opportunities for early life prevention of child and adult cancers, there are diverse opinions about whether there is an adequate evidence base for primary prevention of cancer; in a summary of expert opinion on what evidence should be necessary to support taking action, suggestions range from animal studies and toxicologic profiles to high quality systematic reviews (page 342, left, last bridge paragraph).
Mejia-Arangure teaches the types of acute leukemia (AL) in children are heterogeneous diseases with different etiology, and, therefore, their prevention may be diverse and complex. Improved prevention not only depends on identifying the relevant risk factors associated with the types of AL but also on identifying the patients who are at higher risk of developing the disease and in whom the prevention measures could be more useful (page 1, 1st paragraph); it is clear that the etiology of the types of AL depends on genetic susceptibility, including constitutional susceptibility (e.g., Down syndrome), and is also related to carcinogenic metabolism of immunity to different infectious agents (page 1, last paragraph).
Moreover, Emory Winship Cancer Institute teaches little is known about what exactly causes leukemia and because we don’t know exactly what causes leukemia, the National Cancer Institute doesn’t make specific suggestions on how to prevent it (Full document).
These articles plainly demonstrate that the art of developing and testing preventative therapies for leukemia, particularly for use in humans, is extremely unpredictable.
2. The breadth of the claims
Claims 5-18 and 29 are narrow in terms of the type of diseases being treated and/or prevented and agents utilized, leukemia with 5-chloro-2-(N-((1S,2R)-2-(6-fluoro-2,3-dimethylphenyl)-1-(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)propyl)sulfamoyl)benzamide. Given that even after the effective filing date of the invention it was known that leukemia are heterogeneous diseases with different etiology and their prevention is diverse and complex with no clear agreed upon risk factors or causes, the art establishes that prevention of leukemia is extremely unpredictable.
3. The amount of direction or guidance provided and the presence or absence of working examples
The specification provides data for Compound A in subjects having relapsed or refractory acute myeloid leukemia. The data provided supports evidence of Compound A treating relapsed or refractory acute myeloid leukemia but does not provide any evidence of Compound A preventing any leukemia.
The specification provides no particular direction or guidance for determining the particular administration regimens (e.g., timing, administration routes, etc.) necessary to treat all of the various diseases encompassed by the claims, particularly in humans. The specification discusses a specific daily dosing for one week followed by a resting period of one week but does not discuss amounts that should be administered daily. While the state of the art is that Compound 4 is useful in a method of treating leukemia, there is no experimentation or mechanism of action presented or discussed in the specification regarding the prevention of leukemia.
4. The quantity of experimentation necessary
Because of the known unpredictability of the art (as discussed supra) and in the absence of experimental evidence commensurate in scope with the claims, the skilled artisan would not accept that 5-chloro-2-(N-((1S,2R)-2-(6-fluoro-2,3-dimethylphenyl)-1-(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)propyl)sulfamoyl)benzamide could be predictably used to prevent leukemia.
Genentech Inc. vs. Nova Nordisk states, "[A] patent is not a hunting license. It is not a reward for a search but a compensation for its successful conclusion and 'patent 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" (42 USPQ 2d 1001, Fed. Circuit 1997).
As noted above, the specification provides no experimental support for the prevention of leukemia. A review of the state of the art fails to reveal that any compound is useful as preventative for leukemia. The state of the art is that leukemia are heterogeneous diseases with different etiology and their prevention is diverse and complex with no clear agreed upon risk factors or known causes.
Without clear agreed upon risk factors or known causes determining if any particular claimed compound would prevent leukemia would require synthesis of the compound, formulation into a suitable dosage form, and subjecting it to clinical trials or to testing in an assay known to correlate to clinical efficacy of such treatment. This is undue experimentation given the limited guidance and direction provided by Applicants.
Accordingly, claims 5-18 and 29 do not comply with the enablement requirement of 35 U.S.C. 112(a), since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
Response to Arguments
Since a new rejection was issued (see above), it is the Examiner’s belief that most of the arguments presented by Applicant have been considered/answered in the rejection itself.
Modified Objections and/or Rejections
Modifications Necessitated by Claim Amendment
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.
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.
Claims 5-17, 19-24, and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Miyahara et al (CA 3,025,887, cited in the IDS filed September 19, 2025) in view of Gojo et al (Leukemia Research, 2007; 31:1165-1173, cited in the IDS filed September 19, 2025).
Regarding claims 5, 16, 19, and 22, Miyahara teaches a method of treating tumors comprising administering an effective amount of a compound to a subject in need thereof (claim 33), wherein the compound includes Compound 4, 5-chloro-2-(N-((1S,2R)-2-(6-fluoro-2,3-dimethylphenyl)-1-(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)propyl)sulfamoyl)benzamide (claim 18). Moreover, Miyahara teaches the compound of the present invention has an inhibitory activity against RNR (ribonucleotide reductase) ([0002] and [0129]); useful as a medicament for treatment of RNR-related diseases [0129]; such as malignant tumors including hematopoietic tumors including leukemia [0129]. Thus, Miyahara teaches a method of treating an RNR-related disease, leukemia, in a patient in need thereof comprising administering Compound 4, which is equivalent to the claimed compound.
Miyahara does not explicitly teach the claimed dosing regimen of instant claims 5-14, 19, and 22.
However, Gojo teaches a phase I and pharmacokinetic study of Triapine®, a potent ribonucleotide reductase inhibitor, in adults with advanced hematologic malignancies (title); a Phase I study of Triapine administered as a 2 h infusion for 5 days in 25 adults with advanced leukemias was conducted, Triapine at 96 mg/m2 once a day can be given safely on days 1–5 and 15–19 or 1–5 and 8–12 of a 4-week cycle (Abstract).
As such, since Miyahara teaches a method of treating an RNR-related disease, leukemia, in a patient in need thereof comprising administering Compound 4 and that Compound 4 is an RNR inhibitor, and since Gojo teaches treating leukemia with an RNR inhibitor where the RNR inhibitor is administered for 5 days (days 1-5, i.e. week 1) and (days 15-19, i.e. week 3) and no drug administered on weeks 2 and 4 of a 4-week cycle, it would have been prima facie obvious to one of ordinary skill in the art to utilize the dosing regimen of an RNR inhibitor for treating leukemia taught by Gojo as a starting point for optimizing the treatment regimen of Compound 4 utilized to treat leukemia since both Miyara and Gojo teach RNR inhibitors are useful for treating RNR-related disease, leukemia and because dosage and treatment regimen are result-effective variables, i.e. a variable that achieves a recognized result. Therefore, the determination of the optimum or workable dosages would have been well within the practice of routine experimentation by the skilled artisan. Furthermore, absent any evidence demonstrating a patentable difference between the compositions and the criticality of the claimed dosage range, the determination of the optimum or workable dosing regimen given the guidance of the prior art would have been generally prima facie obvious to the skilled artisan. Please see MPEP 2144.05 [R-2](II)(A) and In re Aller, 220 F. 2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). ("[W]here the general conditions of claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.").
Regarding claim 15, Miyahara teaches when using the compound of the present invention or a salt thereof as a pharmaceutical, it is optionally formulated with a pharmaceutically acceptable carrier, and various dosage forms can be adopted depending on the prevention or therapeutic purposes, and as the dosage forms include, for example, oral agents, injections, suppositories, ointments, and any of such patches; since the compound of the present invention or a salt thereof has an excellent oral absorbability, oral agents are preferable [0133].
Taken together, all this would result in the practice of the method of claims 5-16, 19, and 22 with a reasonable expectation of success.
Regarding claims 17 and 29, as set forth above, Miyahara teaches a method of treating an RNR-related disease, leukemia, in a patient in need thereof comprising administering Compound 4. Miyahara does not explicitly teach the leukemia is acute myeloid leukemia including relapsed or refractory (R/R) acute myeloid leukemia.
However, Gojo teaches adult patients (≥18 years old) with relapsed/refractory acute leukemias including acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), chronic myeloid leukemia (CML) in accelerated or blast phase, poor-risk (IPSS ≥ 1.5) myelodysplasia (MDS), and aggressive (transformed) myeloproliferative disorder (MPD) for whom no standard therapies were anticipated to result in a durable remission were considered eligible for the study (page 1166, left, last paragraph, 2.1). Moreover, Gojo teaches 25 patients with advanced hematologic malignancies were entered on the study (page 1167, right, last); 20 subjects were diagnosed with AML (Table 1), of 20 patients with acute leukemia, 12 patients (60%) had primary refractory disease, 6 (30%) were in first relapse (4 in refractory relapse), and 2 (10%) patients were in a second relapse (page 1167, right, last bridge paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to modify the method of treating leukemia taught by Miyahara to treat relapsed or refractory (R/R) acute myeloid leukemia, since the prior art teaches the claimed compound is an RNR inhibitor useful for treating leukemia generically and that RNR inhibitors are useful for treating acute myeloid leukemia including relapsed and/or refractory AML.
Taken together, all this would result in the practice of the method of claims 17 and 29 with a reasonable expectation of success.
Regarding claims 20 and 23, Miyahara is silent regarding the use of an additional agent. Thus, it is safe to assume that the compound in the method of Miyahara is a administered as a single agent. Moreover, Gojo teaches Triapine as a single agent. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to administer Compound 4 as a single agent in a method of treating refractory AML with a reasonable expectation of success in view of the teachings of the cited art.
Taken together, all this would result in the practice of the method of claims 20 and 23 with a reasonable expectation of success.
Regarding claims 21 and 24, the cited art does not teach the RNR is administered with one or more additional anti-tumor agents.
However, Gojo teaches exploration of triapine in combination with other chemotherapeutic agents is underway; pre-clinical in vivo data demonstrate synergistic inhibition of L1210 leukemia when triapine is combined with DNA-damaging agents such as etoposide, cisplatin, and doxorubicin.
Thus, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to combine the teachings of the references so as to produce a combination comprising Compound 4 taught by Miyahara to further administer an additional anti-tumor agent, a DNA-damaging agents such as etoposide, cisplatin, and doxorubicin as taught by Gojo. One would have been motivated to do so because of each of the compounds have been individually taught in the prior art to be suitable for the treatment of leukemia. Moreover, the instant situation is amenable to the type of analysis set forth in In re Kerkhoven, 205 USPQ 1069 (CCPA 1980) wherein the court held that it is prima facie obvious to combine two agents each of which is taught by the prior art to be useful for the very same purpose. The idea of combining them flows logically from having been individually taught in the prior art. Applying the same logic to the instant claims, one of ordinary skill in the art would have been imbued with at least a reasonable expectation of success that by combining Compound 4 with a DNA-damaging agent, one would have achieved a composition useful for treating leukemia.
Secondly, the strongest rationale for combining references is a recognition, expressly or implicitly in the prior art or drawn from a convincing line of reasoning based on established scientific principles or legal precedent, that some advantage or expected beneficial result would have been produced by their combination. In re Sernaker, 702 F.2d 989, 994-995, 217 USPQ 1, 5-6 (Fed. Cir. 1983). In the instant case, the prior art teaches that the combination of an RNR inhibitor agent with a DNA damaging agent has been shown to demonstrate synergistic inhibition in leukemia. Accordingly, the skilled artisan would expect a superior beneficial result from a combination of Compound 4 and a DNA-damaging agent, given that a combination of an RNR inhibitor compound and a DNA-damaging agent are taught to demonstrate a synergistic effect in vivo in leukemia.
Taken together, all this would result in the practice of the method of claims 21 and 24 with a reasonable expectation of success.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Miyahara et al (CA 3,025,887, cited in the IDS filed September 19, 2025) in view of Gojo et al (Leukemia Research, 2007; 31:1165-1173, cited in the IDS filed September 19, 2025) as applied to claims 5-17, 19-24, and 29 above, and further in view of Micklem et al (WO 2016/075309 A1, cited in the IDS filed December 13, 2024).
Miyara and Gojo teach a method of treating AML comprising administering Compound 4 in a dosing regimen that renders the instantly claimed dosing regimen obvious (see 103 above). The cited art does not teach the AML is SLFN11-positive tumor.
However, Micklem teaches SLFN11 is a biomarker of AML (Title); EMT is increasingly understood to play a key role in cancer metastasis (page 5, line 16); as well as this role in increasing metastatic potential, the EMT program has recently been linked with Cancer Stem Cells (CSCs); these cells were first identified in acute myelocytic leukemia (AML), and have been postulated to represent a subset of tumour cells with stem cell characteristics - i.e. the ability to give rise to all the cell types found in a particular cancer, and thus the ability to form a new tumour; although they may represent only a tiny fraction of the cells in a tumour, CSCs are thought to be particularly resistant to existing anti-cancer drugs; even though drug treatment may kill the vast majority of cells in the tumour, a single surviving CSC can therefore lead 5 to a relapse of the disease; recent evidence suggests an overlap between EMT and CSC phenotypes, suggesting that EMT may also play a role in recurrence of cancer after chemotherapy and the development of drug-resistant tumours in cancer, including AML Robust biomarkers for the EMT phenotype would be useful in identifying patients at particular risk of developing metastatic or drug-resistant cancer, while novel drugs that target cells that have undergone EMT will reduce metastasis and relapse following conventional therapy (page 5, line 30 – page 6 line 14).
Moreover, Micklem teaches a method of identifying a subject having a particular risk of developing metastatic or drug-resistant cancer, comprising assessing the level of expression or activity of Slfn11 in a subject or in a sample derived from the subject, an increased level of Slfn11 expression or activity indicating an increased risk of the subject developing metastatic or drug-resistant cancer (claim 2).
As such, since Miyara and Gojo teach a method of treating AML comprising administering Compound 4, and since Micklem teaches that SLFn11 is a biomarker of AML and is useful for identifying subjects at risk of developing metastatic or drug-resistant cancer, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of treating AML comprising administering Compound 4 suggested by Miyahara and Gojo to treat SLFN11 positive AML with a reasonable expectation of success since the prior art with an expectation of success, since the prior art establishes that Slfn11 is a biomarker of AML and would be useful for identifying subjects at risk of developing metastatic or drug-resistant cancer.
Taken together, all this would result in the practice of the method of claim 18 with a reasonable expectation of success.
Response to Arguments
Applicant argues:
Gojo's disclosure of dose regimen of Triapine does not teach or suggest anything about dose regimen of the claimed compound, which is completely different compound having different mechanism of action. Thus, a person skilled in the art would not modify Miyahara to set or modify dose regimen in view of the disclosure of Gojo, with reasonable expectation of success. Further, Gojo shows several dosing regimens in Table 2, but none of them discloses "daily dosing for one week, followed by a resting period of one week" of claim 1. Gojo discloses that the longer resting period resulted in rebound in blast counts and moved on to continuous administration for two consecutive weeks. Accordingly, Gojo does not teach "a resting period of one week", and does not provide any motivation for a person skilled in the art to try the dose regimen of "daily dosing for one week, followed by a resting period of one week" with reasonable expectation of success, if not teaching away from such dose regimen.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
The Examiner acknowledges that Miyara does not teach the claimed dosing regimen and that Gojo teaches a structurally different RNR inhibitor. However, as set forth above, both Miyara and Gojo teach treating leukemia comprising administering an RNR inhibiter. As set forth above, it would have been prima facie obvious to one of ordinary skill in the art to utilize the dosing regimen of an RNR inhibitor for treating leukemia taught by Gojo as a starting point for optimizing the treatment regimen of Compound 4 utilized to treat leukemia since both Miyara and Gojo teach RNR inhibitors are useful for treating RNR-related disease, leukemia and because dosage and treatment regimen are result-effective variables, i.e. a variable that achieves a recognized result. Therefore, the determination of the optimum or workable dosages would have been well within the practice of routine experimentation by the skilled artisan. Furthermore, absent any evidence demonstrating a patentable difference between the compositions and the criticality of the claimed dosage range, the determination of the optimum or workable dosing regimen given the guidance of the prior art would have been generally prima facie obvious to the skilled artisan. Please see MPEP 2144.05 [R-2](II)(A) and In re Aller, 220 F. 2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). ("[W]here the general conditions of claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.").
Applicant argues:
Micklem was only cited regarding SLFN11 of claim 11, and does not cure the deficiency of Miyahara and Gojo.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
Applicant has not independently argued the merits of this rejection. Arguments regarding Miyahara and Gojo have been addressed above. Therefore, the rejection is maintained for the reasons set forth on the record and for those set forth in the response to the arguments 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 5-24 and 29 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-40 of U.S. Patent No. US 11,634,395 B2 in view of Miyahara et al (CA 3,025,887, cited in the IDS filed September 19, 2025) and Gojo et al (Leukemia Research, 2007; 31:1165-1173, cited in the IDS filed September 19, 2025).
The instant claims are directed to a method of preventing and/or treating leukemia in a patient in need thereof comprising administering an effective amount of 5-chloro-2-(N-((1S,2R)-2-(6-fluoro-2,3-dimetylphenyl)-1-(5-oxo-4,5- dihydro-1,3,4-oxadiazol-2-yl)propyl)sulfamoyl)benzamide or a salt thereof to the patient on an intermittent administration schedule for two weeks comprising dosing 1 to 5 days per week.
The previously allowed claims are directed to a method of treating a tumor by inhibiting ribonucleotide reductase in a subject in need thereof comprising administering an effective amount of a compound of formula (I); wherein the tumor is hematopoietic tumor, wherein the compound of formula (I) is (4) 5-chloro-2-(N-((1S,2R)-2-(6-fluoro-2,3-dimetylphenyl)-1-(5-oxo-4,5- dihydro-1,3,4-oxadiazol-2-yl)propyl)sulfamoyl)benzamide. The copending claims do not explicitly teach the hematopoietic tumor is leukemia or that compound 4 is administered in the claimed dosing regimen.
However, Miyahara teaches a method of treating an RNR-related disease, leukemia, in a patient in need thereof comprising administering Compound 4.
Gojo teaches a phase I and pharmacokinetic study of Triapine®, a potent ribonucleotide reductase inhibitor, in adults with advanced hematologic malignancies (title); a Phase I study of Triapine administered as a 2 h infusion for 5 days in 25 adults with advanced leukemias was conducted, Triapine at 96 mg/m2 once a day can be given safely on days 1–5 and 15–19 or 1–5 and 8–12 of a 4-week cycle (Abstract).
As such, since Miyahara teaches a method of treating an RNR-related disease, leukemia, in a patient in need thereof comprising administering Compound 4 and that Compound 4 is an RNR inhibitor, and since Gojo teaches treating leukemia with an RNR inhibitor where the RNR inhibitor is administered for 5 days (days 1-5, i.e. week 1) and (days 15-19, i.e. week 3) and no drug administered on weeks 2 and 4 of a 4-week cycle, it would have been prima facie obvious to one of ordinary skill in the art to modify the method of the previously allowed claims to treat leukemia and to utilize the dosing regimen of an RNR inhibitor for treating leukemia taught by Gojo as a starting point for optimizing the treatment regimen of Compound 4 utilized to treat leukemia since both Miyara and Gojo teach RNR inhibitors are useful for treating RNR-related disease, leukemia and because dosage and treatment regimen are result-effective variables, i.e. a variable that achieves a recognized result. Therefore, the determination of the optimum or workable dosages would have been well within the practice of routine experimentation by the skilled artisan. Furthermore, absent any evidence demonstrating a patentable difference between the compositions and the criticality of the claimed dosage range, the determination of the optimum or workable dosing regimen given the guidance of the prior art would have been generally prima facie obvious to the skilled artisan. Please see MPEP 2144.05 [R-2](II)(A) and In re Aller, 220 F. 2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). ("[W]here the general conditions of claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.").
Thus resulting in the practice of the method of the instant claims.
Claims 5-24 and 29 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 16, 21, 23, 24-30, 32, and 35-44 of U.S. Application No. 16/767,306 in view of Miyahara et al (CA 3,025,887, cited in the IDS filed September 19, 2025) and Gojo et al (Leukemia Research, 2007; 31:1165-1173, cited in the IDS filed September 19, 2025).
The instant claims are directed to a method of preventing and/or treating leukemia in a patient in need thereof comprising administering an effective amount of 5-chloro-2-(N-((1S,2R)-2-(6-fluoro-2,3-dimetylphenyl)-1-(5-oxo-4,5- dihydro-1,3,4-oxadiazol-2-yl)propyl)sulfamoyl)benzamide or a salt thereof to the patient on an intermittent administration schedule for two weeks comprising dosing 1 to 5 days per week.
The copending claims are directed to a method of treating a tumor in a subject in need thereof comprising administering an effective amount of a sulfonamide compound, (2) 5-chloro-2-(N-((1S,2R)-2-(6-fluoro-2,3-dimetylphenyl)-1-(5-oxo-4,5- dihydro-1,3,4-oxadiazol-2-yl)propyl)sulfamoyl)benzamide and at least one other antitumor agent. The copending claims do not explicitly teach a tumor is leukemia or that compound 2 is administered in the claimed dosing regimen.
However, Miyahara teaches a method of treating an RNR-related disease, leukemia, in a patient in need thereof comprising administering Compound 4.
Gojo teaches a phase I and pharmacokinetic study of Triapine®, a potent ribonucleotide reductase inhibitor, in adults with advanced hematologic malignancies (title); a Phase I study of Triapine administered as a 2 h infusion for 5 days in 25 adults with advanced leukemias was conducted, Triapine at 96 mg/m2 once a day can be given safely on days 1–5 and 15–19 or 1–5 and 8–12 of a 4-week cycle (Abstract).
As such, since Miyahara teaches a method of treating an RNR-related disease, leukemia, in a patient in need thereof comprising administering Compound 4 and that Compound 4 is an RNR inhibitor, and since Gojo teaches treating leukemia with an RNR inhibitor where the RNR inhibitor is administered for 5 days (days 1-5, i.e. week 1) and (days 15-19, i.e. week 3) and no drug administered on weeks 2 and 4 of a 4-week cycle, it would have been prima facie obvious to one of ordinary skill in the art to modify the method of the previously allowed claims to treat leukemia and to utilize the dosing regimen of an RNR inhibitor for treating leukemia taught by Gojo as a starting point for optimizing the treatment regimen of Compound 4 utilized to treat leukemia since both Miyara and Gojo teach RNR inhibitors are useful for treating RNR-related disease, leukemia and because dosage and treatment regimen are result-effective variables, i.e. a variable that achieves a recognized result. Therefore, the determination of the optimum or workable dosages would have been well within the practice of routine experimentation by the skilled artisan. Furthermore, absent any evidence demonstrating a patentable difference between the compositions and the criticality of the claimed dosage range, the determination of the optimum or workable dosing regimen given the guidance of the prior art would have been generally prima facie obvious to the skilled artisan. Please see MPEP 2144.05 [R-2](II)(A) and In re Aller, 220 F. 2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). ("[W]here the general conditions of claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.").
Thus resulting in the practice of the method of the instant claims. This is a provisional nonstatutory double patenting rejection.
Claims 5-24 and 29 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 14 and 16-31 of U.S. Application No. 17/614,074 (Notice of Allowance mailed February 18, 2026) in view of Miyahara et al (CA 3,025,887, cited in the IDS filed September 19, 2025) and Gojo et al (Leukemia Research, 2007; 31:1165-1173, cited in the IDS filed September 19, 2025).
The instant claims are directed to a method of preventing and/or treating leukemia in a patient in need thereof comprising administering an effective amount of 5-chloro-2-(N-((1S,2R)-2-(6-fluoro-2,3-dimetylphenyl)-1-(5-oxo-4,5- dihydro-1,3,4-oxadiazol-2-yl)propyl)sulfamoyl)benzamide or a salt thereof to the patient on an intermittent administration schedule for two weeks comprising dosing 1 to 5 days per week.
The copending claims are directed to a method for treating and/or preventing a tumor comprising administering an effective amount of a sulfonamide compound of Formula (I) in combination with an immune checkpoint molecule regulator, wherein the compound of Formula (I) is (2) 5-chloro-2-(N-((1S,2R)-2-(6-fluoro-2,3-dimetylphenyl)-1-(5-oxo-4,5- dihydro-1,3,4-oxadiazol-2-yl)propyl)sulfamoyl)benzamide and at least one other antitumor agent. The copending claims do not explicitly teach a tumor is leukemia or that the claimed compound is administered in the claimed dosing regimen.
However, Miyahara teaches a method of treating an RNR-related disease, leukemia, in a patient in need thereof comprising administering Compound 4.
Gojo teaches a phase I and pharmacokinetic study of Triapine®, a potent ribonucleotide reductase inhibitor, in adults with advanced hematologic malignancies (title); a Phase I study of Triapine administered as a 2 h infusion for 5 days in 25 adults with advanced leukemias was conducted, Triapine at 96 mg/m2 once a day can be given safely on days 1–5 and 15–19 or 1–5 and 8–12 of a 4-week cycle (Abstract).
As such, since Miyahara teaches a method of treating an RNR-related disease, leukemia, in a patient in need thereof comprising administering Compound 4 and that Compound 4 is an RNR inhibitor, and since Gojo teaches treating leukemia with an RNR inhibitor where the RNR inhibitor is administered for 5 days (days 1-5, i.e. week 1) and (days 15-19, i.e. week 3) and no drug administered on weeks 2 and 4 of a 4-week cycle, it would have been prima facie obvious to one of ordinary skill in the art to modify the method of the copending claims to treat leukemia and to utilize the dosing regimen of an RNR inhibitor for treating leukemia taught by Gojo as a starting point for optimizing the treatment regimen of Compound 4 utilized to treat leukemia since both Miyara and Gojo teach RNR inhibitors are useful for treating RNR-related disease, leukemia and because dosage and treatment regimen are result-effective variables, i.e. a variable that achieves a recognized result. Therefore, the determination of the optimum or workable dosages would have been well within the practice of routine experimentation by the skilled artisan. Furthermore, absent any evidence demonstrating a patentable difference between the compositions and the criticality of the claimed dosage range, the determination of the optimum or workable dosing regimen given the guidance of the prior art would have been generally prima facie obvious to the skilled artisan. Please see MPEP 2144.05 [R-2](II)(A) and In re Aller, 220 F. 2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). ("[W]here the general conditions of claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.").
Thus resulting in the practice of the method of the instant claims.
This is a provisional nonstatutory double patenting rejection.
Claims 5-24 and 29 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 14 and 16-31 of U.S. Application No. 18/044,978 in view of Gojo et al (Leukemia Research, 2007; 31:1165-1173, cited in the IDS filed September 19, 2025).
The instant claims are directed to a method of preventing and/or treating leukemia in a patient in need thereof comprising administering an effective amount of 5-chloro-2-(N-((1S,2R)-2-(6-fluoro-2,3-dimetylphenyl)-1-(5-oxo-4,5- dihydro-1,3,4-oxadiazol-2-yl)propyl)sulfamoyl)benzamide or a salt thereof to the patient on an intermittent administration schedule for two weeks comprising dosing 1 to 5 days per week.
The copending claims are directed to a method of preventing and/or treating an RNR-related disease in a patient in need thereof, the method comprising administering an effective amount of 5-chloro-2-(N-((1S,2R)-2-(6- fluoro-2,3-dimetylphenyl)-1-(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)propyl)sulfamoyl)benzamide or a salt thereof to the patient on an administration schedule comprising daily dosing for one week, followed by a resting period of one week. Thus, the copending claims teach a method of preventing and/or treating an RNR-related disease in a patient in need thereof, the method comprising administering an effective amount of 5-chloro-2-(N-((1S,2R)-2-(6- fluoro-2,3-dimetylphenyl)-1-(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)propyl)sulfamoyl)benzamide or a salt thereof to the patient on an intermittent administration schedule for two weeks comprising administering 7 days per week and off 7 days. The copending claims do not explicitly teach that the claimed compound is administered in the claimed dosing regimen.
However, Gojo teaches a phase I and pharmacokinetic study of Triapine®, a potent ribonucleotide reductase inhibitor, in adults with advanced hematologic malignancies (title); a Phase I study of Triapine administered as a 2 h infusion for 5 days in 25 adults with advanced leukemias was conducted, Triapine at 96 mg/m2 once a day can be given safely on days 1–5 and 15–19 or 1–5 and 8–12 of a 4-week cycle (Abstract).
It would have been prima facie obvious to one of ordinary skill in the art to utilize the dosing regimen of an RNR inhibitor for treating leukemia taught by the copending claims and Gojo as a starting point for optimizing the treatment regimen of Compound 4 utilized to treat leukemia since Gojo teaches RNR inhibitors are useful for treating RNR-related disease, leukemia and because dosage and treatment regimen are result-effective variables, i.e. a variable that achieves a recognized result. Therefore, the determination of the optimum or workable dosages would have been well within the practice of routine experimentation by the skilled artisan. Furthermore, absent any evidence demonstrating a patentable difference between the compositions and the criticality of the claimed dosage range, the determination of the optimum or workable dosing regimen given the guidance of the prior art would have been generally prima facie obvious to the skilled artisan. Please see MPEP 2144.05 [R-2](II)(A) and In re Aller, 220 F. 2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). ("[W]here the general conditions of claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.").
Thus resulting in the practice of the method of the instant claims.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant argues:
A person of ordinary skill in the art would not have been motivated to combine Miyahara and Gojo or expected success from such a combination. Because Miyahara and Gojo fail to render obvious the pending claims, the double patenting rejections-all of which rely on these two references-also fail to render obvious the pending claims.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
Applicant has not independently argued the merits of this rejection. Arguments regarding Miyahara and Gojo have been addressed above. Therefore, the rejection is maintained for the reasons set forth on the record and for those set forth in the response to the arguments above.
Conclusion
Claims 5-24 and 29 are rejected.
No claim is 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.
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/Rayna Rodriguez/ Primary Examiner, Art Unit 1628