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
Status of 17/771,945
Claims 1, 4, 12-18, 21-27, 29-33, 36, 64, and 67 are currently pending.
Priority
Instant application 17/771,945, filed 4/26/2022, claims priority as follows:
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Priority document 62/926,869 contains support for the instant claims, and thus, claims 1, 4, 12-18, 21-27, 29-33, 36, 64, and 67 are granted the priority date of 10/28/2019.
Information Disclosure Statement
All references from the IDS’s submitted on 6/13/2022 and 5/8/2024 have been considered unless marked with a strikethrough.
Response to Applicants Arguments/Amendments
No arguments or amendments have been filed in response to the rejections raised in the Non-Final dated 4/11/2025. Thus, the rejections raised in the Non-Final dated 4/11/2025 are maintained and now made FINAL.
The Examiner recognizes the content of the Response to Non-Final Office Action filed 10/9/2025, and notes this Final Rejection is a formality. The application will be abandoned upon no response from Applicant in accordance with MPEP § 711.
Election/Restriction
Applicant’s election of Group I, claims 1, 4, 12-18, 21-27, 29-33, 36, and 64, drawn to methods of treating conditions treatable with ERK 1/2 inhibition with compounds of Formula (II), without traverse in the reply filed 3/20/2025 is acknowledged. Applicant’s election of ((S)-N-(2-amino-1-(3-chloro-5-fluoro-phenyl)ethyl)-1-(5-methyl-2-((tetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)-1H-imidazole-4-carboxamide):
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And colorectal cancer in the reply filed 3/20/2025, is also acknowledged.
Examination will begin with the elected species. In accordance with MPEP § 803.02, if upon examination of the elected species, no prior art is found that would anticipate or render obvious the instant invention based on the elected species, the search of the Markush-type claim will be extended. If prior art is then found that anticipates or renders obvious the non- elected species, the Markush-type claim will be rejected. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be examined again. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. In the event prior art is found during further examination that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final.
In the Non-Final dated 4/11/2025, the elected species was searched and prior art was identified. Due to the lack of Applicant’s arguments/amendments filed in response to the Non-Final, the prior art rejection has been maintained and the scope of the search has not been expanded. The full scope of the claims has not yet been searched in accordance with Markush search practice. Claims 1, 4, 12-18, 21-27, 30-31, 36, and 64 read on the elected species. Claims 29, 32-33, and 67 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species and/or group, there being no allowable generic or linking claim.
MAINTAINED REJECTIONS
Claim Rejections - 35 USC § 112(a)
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, 4, 12-18, 21-27, 30-31, 36, and 64 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The courts have stated that, “To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated that, “A written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials.” Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) (“In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus …”) Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed genus is sufficient. See MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case are discussed below.
In the instant case, the claims of the instant application embrace compounds of Formula (II), or a pharmaceutically acceptable salt, prodrug, solvate, hydrate, or stereoisomer thereof. Particularly, the term “prodrug” recited in claims 1, 30, and 31 invoke the 35 U.S.C. 112(a) rejection, and claims 4, 12-18, 21-27, 36, and 64 depend from the above claims. Even a cursory calculation of the number of compounds embraced in the instant claims would result in thousands of compounds.
Level of skill and knowledge in the art
The level of skill and knowledge in the art is high.
Partial Structure
Compounds of Formula (II) have been disclosed and example compound species that would be within the general formula have been disclosed. However, as to the claimed prodrugs, only four representative examples, compounds 135, 150, 158, and 340, qualify as prodrugs in light of the definition disclosed on page 40, lines 31-35 and page 41, lines 1-12 of the specification. The small representative number of examples does not demonstrate possession or put the public in possession of all the claimed prodrugs of Formula (II). It is generally accepted that prodrugs may vary by chemical formulae and may also differ in properties and the arrangement of atoms in the molecule.
Physical and/or chemical properties/functional characteristics
The compounds of Formula (II), and prodrugs thereof, are compounds which are allegedly useful in treatment of conditions treatable by inhibiting ERK 1/2, for example in the treatment of colorectal cancer. Although the art recognizes generally accepted definitions, the terms are not explicitly defined by the specification in such a way as to demonstrate that the inventor had possession of all prodrugs of Formula (II).
A review of the prior art identifies the reference Najjar (Najjar, A. & Karaman, R. Expert Opinion on Drug Discovery, 2018, 14(3), 199-220) which discloses successes and failures of prodrugs of known pharmaceuticals, one example of which is also an ester (abstract and page 212, section 3). Najjar teaches hetacillin, an ester prodrug of ampicillin, which was withdrawn since it did not have a superior advantage when compared to ampicillin. In light of Najjar, it is unknown which of the esters, amides, or prodrugs of compounds of Formula (II) claimed by Applicant is will be active or inactive. Further, one of ordinary skill in the art would not be able to predict which compounds, of the vast number that are claimed, will be active or inactive absent evidence. There is no structure/function correlation in the specification showing which prodrugs would or would not be active.
Applicant has not described which prodrugs have the ability to treat conditions treatable by inhibiting ERK 1/2, and which do not. Stated differently, the small representative number of examples does not provide a structure/function correlation and the specific examples of prodrugs disclosed do not demonstrate which compounds would retain activity. Further, one of ordinary skill in the art would not be able to predict the biological activity of the claimed prodrugs of Formula (II).
Predictability of the art
Medicinal chemistry is an experimental science with a low predictability level. Small changes in the structure of a compound can lead to large differences in their pharmacological activity. Regarding prodrugs, predicting if a certain claimed compound retains the activity and function of the original drug is filled with experimental uncertainty because prodrugs contain variation by chemical and physical properties of the molecules.
Method of making the claimed invention
Although the specification provides a method for making the compounds of Formula (II), the specification solely provides two examples of making prodrugs (page 83) and does not provide methods for making all of the compounds, including the prodrugs, encompassed by the instant claims. Methods of synthesizing compounds are, in general, known to a person of ordinary skill; however, methods of making the myriad of compounds encompassed by the instant claims is beyond the skill of the artisan, particularly when certain elements, such as prodrugs are merely described partially.
As such, the instant specification and instant claims do not provide sufficient description such that one could anticipate what additional elements are present in the prodrugs of Formula (II) because the examples illustrated in the experimental section are limited to only two examples of prodrugs of Formula (II).
Substantial and undue experimentation would be needed to practice Applicant’s invention because the specification lacks sufficient detail to show how to use the prodrugs of the instant invention. Further, there is no guarantee that all of the prodrugs embraced by the scope of the claims would be use in treatment of a condition treatable by inhibiting ERK 1/2, for example in treatment of colorectal cancer.
Even with the undue burden of experimentation, there is no guarantee that one would obtain the product of a desired prodrug of an instant compound of Formula (II). Although some functional characteristics are disclosed or would be known to a person of ordinary skill in the art, in the absence of a representative number of examples, there can be no correlation between the function and structure of the claimed prodrugs in the instant application.
The MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic. It is unquestionable that the claim(s) are broad and generic with respect to all possible compounds encompassed by the claims: the possible structural variations are limitless to any prodrugs of the compound species. In the instant case, however, the specification does not disclose a sufficient variety of species to reflect this variance in the genus. Specification does not provide sufficient descriptive support for the myriad of compounds embraced by the claims such as, for example prodrugs of the Formula (II).
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”) Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Dependent claims 4, 12-18, 21-27, 36, and 64 do not resolve the 112(a) written description rejections raised in claims 1, 30, and 31, since those claims do not further limit or provide further structure of the prodrugs of Formula (II). Accordingly, these claims are also rejected. This rejection would be overcome by amending the claims to remove the term “prodrug”.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 4, 12-18, 21-27, 30-31, 36, and 64 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Asana Biosciences, LLC (US 2016/0362406, cited in the IDS of 6/13/2022, herein after “Asana”).
The instant claims are drawn to methods of treating colorectal cancer, a condition treatable by inhibiting ERK 1/2, with a therapeutically effective amount of the elected species of about 80 mg to about 350 mg. This rejection applies to the elected species.
The reference Asana discloses heterocyclic compounds useful for inhibiting ERK 1/2 (abstract) and methods of treating a condition treatable by inhibiting ERK 1/2 with said compounds (claims 26 and 27). Specifically, Asana discloses example 24, also referenced as compound #275 (page 77):
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Which anticipates the elected species and a compound instant formula (II):
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When R4 is a 6-membered heterocyclyl, Z is N, R5 is C1 alkyl, X is CH, Y is N, R6 is H, M is a bond, R3 is H, R2 is amino-C1 alkyl, R8 is H, n is 0, and R1 is C6 aryl substituted with 2 halogen substituents.
Asana discloses a method of treating colorectal cancer cell lines, HT29 and HCT116, in mouse xenografts with compound #275 (page 154, para [0693] and page 156, Table 2). Further, Asana discloses the therapeutically effective amounts may be provided on a regular schedule, including weekly (page 25, para [0351]), and the therapeutically effective amount may range from about 0.01 mg/kg, to about 500 mg/kg (page 25, para [0350]), which depending on the weight of the subject anticipates the dosing limitation of about 80 mg to 350 mg.
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 1, 4, 12-18, 21-27, 30-31, 36, and 64 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18, 20-21, and 26-27 of U.S. Patent No. 9,896,445. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘445 patent teach compounds of Formula (II), including the elected species, methods of inhibiting ERK 1/2 with said compounds, and methods of treating a condition treatable by inhibiting ERK 1/2, such as cancer. Regarding the compound claims, the utility disclosed in the instant specification provides further support for a nonstatutory double patenting rejection. See MPEP § 804(I)(B)(1) and Sun Pharm. Indus., Ltd. v. Eli Lilly & Co., 611 F.3d 1381, 95 USPQ2d 1797 (Fed. Cir. 2010).
Claims 1, 4, 12-18, 21-27, 30-31, 36, and 64 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18, 20-21, 26, 29, 32-33, and 35-38 of U.S. Patent No. 10,471,051. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘051 patent teach methods of treating a disease or condition, such as colorectal cancer, with compounds of Formula (II), including the elected species.
Claims 1, 4, 12-18, 21-27, 30-31, 36, and 64 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, and 5 of U.S. Patent No. 11,103,491. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘491 patent teach the elected species. The utility disclosed in the instant specification provides further support for a nonstatutory double patenting rejection. See MPEP § 804(I)(B)(1) and Sun Pharm. Indus., Ltd. v. Eli Lilly & Co., 611 F.3d 1381, 95 USPQ2d 1797 (Fed. Cir. 2010).
Claims 1, 4, 12-18, 21-27, 30-31, 36, and 64 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-5, and 9-11 of U.S. Patent No. 11,925,629. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘629 patent recite methods of inhibiting ERK 1/2 and treating colorectal cancer with the elected species.
Claims 1, 4, 12-18, 21-27, 30-31, 36, and 64 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 36, 77, and 82 of copending Application No. 18/570,818. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘818 application recite a method of treating cancer with the elected species, including the limitations of colorectal cancer, weekly administration, and an amount of about 25 mg/day and about 300 mg/day.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1, 4, 12-18, 21-27, 30-31, 36, and 64 are rejected. Claims 29, 32-33, and 67 are withdrawn.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kendall Heitmeier whose telephone number is (703)756-1555. The examiner can normally be reached Monday-Friday 8:30AM-5:00PM ET.
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/K.N.H./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621