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 .
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.
Current Status of 17/506,959
This office action is in response to the amended claims on 8 December 2025.
Claim 1-2 and 20 are previously presented; and claims 3-19 are original.
Examiner have maintained 102 rejections with modification.
Examiner is maintaining 112 (a) enablement rejections and 103 obvious rejection with modification.
Claims 1-20 are examined in this office action.
Priority
The effective filing date is 04/22/2019 since the instant claims find support in provisional application no. 62/837,049.
Response to Arguments
Examiner acknowledges the receipt of applicant’s claim amendment and remarks of 12/08/2025. Examiner have reviewed these remarks and amendments.
Regarding 112 (a) rejection,
Applicant Argues:
Species have written support, stating specification siRNA have different structures from small molecule inhibitors and act on ERK5 via a different mechanism. This supports that ERK5 inhibitors known in the art would be effective for treating pediatric H3K27M-glioma. A skilled person would be capable of selecting an ERK5 inhibitor without undue experimentation.
Examiner response:
Examiner disagrees, all ERK5 inhibitors are not structurally same, for example
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(BIX02189) is different than
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(ERK5-in1) inhibitor therefore the mechanism by which siRNA is effected maybe different for different ERK5 inhibitors, therefore applicant’s argument is not persuasive. Examiner interprets applicant traversal as attorney opinion therefore does not advance prosecution toward allowance. Therefore 112(a) rejection is maintained.
Please note a claim cannot be allowed for claiming the invention in the negative, for example claim 1 recites “…wherein ERK5 inhibitor is not (16E)-14-methyl-20-oxa-5,7,14,26- tetraazatetracyclo[ 19.3.1.1(2,6).1(8,12)]-heptacosa-1(25),2(26),3,5,8(27),9,11,16,21,23 -decaene (TG02) or a pharmaceutically acceptable salt thereof;…” Applicant is advised to strike this phrase from claim 1 to advance prosecution.
Regarding 102 rejection:
Applicant argues:
Rullion doesn’t explicitly disclose glioma as H3K27M mutant, therefore 102 rejection should be withdrawn.
Examiner response:
Examiner disagrees, REUILLON do not explicitly disclose the type of glioma therefore examiner used broadest reasonable interpretation for pediatric glioma as H3K27M mutant glioma. Moreover, there is evidence that 80% of pediatric glioma are H3K27M mutant (abstract, Nazarian J. H3K27M mutant glioma: Disease definition and biological underpinnings. Neuro Oncol. 2024 May 3;26) Therefore 102 rejection is maintained.
Regarding 103 rejection:
Applicant argues:
H3K27K mutant glioma exhibit increased susceptibility to ERK5 inhibitors in comparison to H3-Wildtype glioma. Which indicate surprising and unexpected result (remarks, page 6-7).
Examiner response:
Examiner disagrees, there is evidence that 80% of pediatric glioma are a result of H3K27M mutant glioma (abstract, Nazarian J. H3K27M mutant glioma: Disease definition and biological underpinnings. Neuro Oncol. 2024 May 3;26) REUILLON teaches a method of treating pediatric glioma with ERK5 inhibitor therefore examiner used broadest reasonable interpretation to interpret pediatric glioma as H3K27M mutant glioma (see maintained 102 and 103 rejection below). Therefore, H3K27K mutant glioma exhibiting increased susceptibility to ERK5 inhibitors in comparison to H3-Wildtype glioma, does not change the scope of the rejection on file. Wu et. al. teaches H3K27K mutant glioma. Therefore 103 rejection is maintained with modification.
Claim Rejections - 35 USC § 112(maintained)
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 1-3, 5 and 7-20 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 TG-02, ERK5-IN-1, BIX02189 and XMD8-92 for treating pediatric glioma, does not reasonably provide enablement for use of any ERK5 inhibitor to treat H3K27M-mutant glioma as required by instant claim 1, which permits any ERK5 inhibitor that is not TG02. 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.
Factors to be considered in making the determination as to whether one skilled in the art would recognize that the applicant was in possession of the claimed invention as a whole at the time of filing include:
(a) Breadth of the claims:
(b) Nature of the invention;
(c) State of the prior art;
(d) Level of one of ordinary skill;
(e) level of predictability art
(f) amount of direction provided by the inventor;
(g) existence of working examples;
(h)and Quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The instant claims are drawn very broadly to plurality of species within the broad genus ERK5 inhibitors used for treating pediatric H3K27M mutant glioma (claims 1-3, 5 and 7-19) without providing enablement for this plurality of ERK5 inhibitors. For example, experiments in the disclosure supports TG-02, ERK5-IN-1, BIX02189 and XMD8-92 being used to treat H3K27M-glioma but do not support vast number of ERK5 inhibitors found in prior art (see MedChemExpress, previously provided to Applicants). Therefore, a person skill in the art would not be able to conclude all ERK5 inhibitors can be used for treating pediatric H3K27M-glioma without further and undue experimentation/investigation. Moreover, the missing guidance cannot easily be predicted by an artisan skilled in the art. Therefore, specification does not provide support for the full scope of instant claims 1 and 20.
Applicant can overcome enablement rejection by narrowing the scope of invention within instant claims 1 and 20 to ERK5-IN-1, BIX02189 and XMD8-92, being used to treat H3K27M-glioma. This is why instant claims 4 and 6 are not rejected in this scope of enablement rejection.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
Claim Rejections - 35 USC § 102(maintained with modification)
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.
Claim(s)1-3,5, 7-9 and 15-19 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by REUILLON; Tristan et. al. (US-20180170911-A1) with evidentiary reference of (Nazarian J. et.al. H3K27M mutant glioma: Disease definition and biological underpinnings. Neuro Oncol. 2024 May 3;26).
Nazarian et.al teaches 80% of pediatric glioma are H3K27M mutant (abstract,). REUILLON; Tristan et. al. discloses a method for treating a glioma in a pediatric human subject [0026] (examiner interpret this as H3K27K-mutant glioma, since reuillon is silent on type of glioma, thus teaching claims 1-2) methods for the prophylaxis or treatment of a disease or condition as described herein; [0033] comprising administering intermittently [0410] (claim 15) to the subject orally[0412](claim 7) a therapeutically effective amount in the amount of 2mg-200mg ([0412] claims 8-9) of an ERK5 inhibitor(prior art is silent on ERK5 inhibitor is ERK5 specific inhibitor, therefore examiner interpret this as ERK5 specific inhibitor, thus anticipating claim 3) , wherein the ERK5 inhibitor is not (16E)-14-methyl-20-oxa-5, 7, 14,26-tetraazatetracyclo[1 9.3.1.1 (2,6).1 (8, 12)]-heptacosa-1 (25),2(26),3,5,8(27),9, 11, 16,21,23-decaene (TG02) or a pharmaceutically acceptable salt thereof [0026] thus teaching claim 1 and 18-19. REUILLON; Tristan et. al. also discloses compound for treatment can be used in conjunction with radiotherapy [0505] teaching claims 16-17.
REUILLON; Tristan et. al. teaches ERK5 is phosphorylated by Mitogen - activated protein kinase 5, (MEK5)(also known as MAP2K5 , MAPKK5 ) MEK5 is the upstream activator of ERK5 in many epithelial cells . In one embodiment the compounds of the invention of REUILLON; Tristan et. al. may also inhibit MEK5. In one embodiment the compounds of the invention may be dual MEK5 / ERK5 inhibitors [0323] (examiner interpret this as dual ERK5 inhibitor) (claim 5).
Nazarian et.al teaches 80% of pediatric glioma are caused by H3K27M mutation (abstract,) (claim 1 and 2). Reuillon et. al. discloses a method for treating a glioma in a pediatric human subject [0026]. Therefore, Reuillon is relied upon for the beneficial teaching of Nazarian that the 80% of pediatric glioma are caused by H3K27M mutation which anticipates claims 1-3,5 7-9 and 15-19.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
Claim Rejections - 35 USC § 103(maintained with modification)
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 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over
REUILLON; (US-20180170911-A1) with evidentiary reference of (Nazarian J. et.al. H3K27M mutant glioma: Disease definition and biological underpinnings. Neuro Oncol. 2024 May 3;26)
In view of
Wu et. al. Nat Genet.; 2012 September 01, 44(3): 251–253
In further view of
Knapp et. al. (European Journal of Medicinal Chemistry 70 (2013) 758-767).
1. Determining the scope and contents of the prior art.
Independent claim 1 is drawn to method of treatment of pediatric glioma with ERK5 inhibitor, REUILLON; Tristan et. al. (US-20180170911-A1) with evidentiary reference of (Nazarian J. et.al. H3K27M mutant glioma: Disease definition and biological underpinnings. Neuro Oncol. 2024 May 3;26) teaches claim(s)1-3,5, 7-9 and 15-19(see above). Independent claim 20 is drawn to a kit containing the limitations of instant claim 1.
Wu et.al teaches a glioma with H3K27K mutant pediatric glioma in children (page 2) (claim 2).
Knapp et.al discloses ERK5-IN-1(applicant’s elected species) as a potent ERK5 inhibitor(abstract) (ERK5 specific inhibitor, claim 3) teaching claim 4.
2. Ascertaining the differences between the prior art and the claims at issue.
Reuillon et.al. does not teach a method of treating H3K27K mutant pediatric glioma in children with ERK5-IN-1.
Wu et. al. does not teach a method of treating H3K27K mutant pediatric in children with ERK5-IN-1.
Knapp et.al does not teach a method of treating H3K27K mutant pediatric in children with ERK5-IN-1.
3. Resolving the level of ordinary skill in the pertinent art.
The level of ordinary skill in the art is an artisan who is versed in developing method of treatment of glioma and looking into developing treatment method for pediatric glioma with ERK5-inhibitor.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
One skilled in the art would be motivated to develop a method of treating pediatric glioma with H3K27K mutant pediatric glioma(Wu et.al page 2) (claim 2) by administering ERK5 inhibitor, wherein the ERK5 inhibitor is not (16E)-14-methyl-20-oxa-5, 7, 14,26-tetraazatetracyclo [1 9.3.1.1 (2,6).1 (8, 12)]-heptacosa-1 (25),2(26),3,5,8(27),9, 11, 16,21,23-decaene (TG02) or a pharmaceutically acceptable salt thereof (Reuillon et.al. [0026]). Since ERK5 inhibitor is used to treat pediatric treat glioma (Reuillon et. al. [0317]) it would be expected ERK5 inhibitor can also treat pediatric glioma with H3K27K mutant pediatric glioma. Moreover, artisan would be motivated to develop a method of treating pediatric glioma with H3K27K mutant pediatric glioma(Wu et.al page 2) (Wu et.al page 251) with ERK5-IN-I(Knapp et.al page abstract), since ERK5-IN-I is a known ERK5 inhibitor and is also expected to treat pediatric glioma with H3K27K mutant pediatric glioma.
Similarly, BIX02189 and XMD8-92 are also ERK5 inhibitor as per claim construction, therefore BIX02189 and XMD8-92 are also expected to treat H3K27K mutant pediatric glioma thus teaching BIX02189 and XMD8-92
Claim 20 is directed to a kit for with the limitation recited in claim 1 thus claim 20 prima facia obvious (MPEP 2112.01(I). Also, a “kit claim” (claim 20) is not patentably distinguishable from prior art otherwise teaching the use of ERK5 inhibitor, supra. “Where the only difference between a prior art product and a claimed product is printed matter that is not functionally related to the product, the content of the printed matter will not distinguish the claimed product from the prior art. In re Ngai, 367 F.3d 1336, 1339, 70 USPQ2d 1862, 1864 (Fed. Cir. 2004).” See MPEP 2112.01(III). Thus, teaching claims 1-5, 7-9 and 15-20.
Therefore, it is prima facia obvious to combine the teaching of REUILLON; Tristan et. al. (US-20180170911-A1); Wu et. al. Nat Genet.; 44(3): 251–253; and Knapp et. al. (European Journal of Medicinal Chemistry 70 (2013) 758-767) to develop a method of treatment of pediatric H3K27K mutant pediatric glioma with ERK5-IN-I.
Claims 8-11 are directed to dosage and claims 12-14 are directed method of administration of drugs. Examiner interprets these attributes as variables the artisan would normally be expected to routinely optimize. For example, dosage of pharmaceuticals are routinely optimized based on body weight and body surface area (Anisel et.al. "PHARMACEUTICAL DOSAGE FORMS AND DRUG DELIVERY SYSTEMS" 7th edition, Year: 1999) Generally, dosage and method of administration of drugs will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such attributes are critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969). See MPEP 2144.05(II)(A). Thus, teaching claims 8-14.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
Conclusion
Claims 1-20 are rejected.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/R.I./Examiner, Art Unit 1625
/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625
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