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 .
Current Status
This action is responsive to the amended claims of 12/07/2023. Claims 1-26 and 29 are pending. Claims 6-7, 11, and 13 are withdrawn. Claims 1-5, 8-10, 12, 14-26, and 29 have been examined on the merits.
Election/Restriction
REQUIREMENT FOR UNITY OF INVENTION
As provided in 37 CFR 1.475(a), a national stage application shall relate to one invention only or to a group of inventions so linked as to form a single general inventive concept (“requirement of unity of invention”). Where a group of inventions is claimed in a national stage application, the requirement of unity of invention shall be fulfilled only when there is a technical relationship among those inventions involving one or more of the same or corresponding special technical features. The expression “special technical features” shall mean those technical features that define a contribution which each of the claimed inventions, considered as a whole, makes over the prior art.
The determination whether a group of inventions is so linked as to form a single general inventive concept shall be made without regard to whether the inventions are claimed in separate claims or as alternatives within a single claim. See 37 CFR 1.475(e).
When Claims Are Directed to Multiple Categories of Inventions:
As provided in 37 CFR 1.475 (b), a national stage application containing claims to different categories of invention will be considered to have unity of invention if the claims are drawn only to one of the following combinations of categories:
(1) A product and a process specially adapted for the manufacture of said product; or
(2) A product and a process of use of said product; or
(3) A product, a process specially adapted for the manufacture of the said product, and a use of the said product; or
(4) A process and an apparatus or means specifically designed for carrying out the said process; or
(5) A product, a process specially adapted for the manufacture of the said product, and an apparatus or means specifically designed for carrying out the said process.
Otherwise, unity of invention might not be present. See 37 CFR 1.475 (c).
Election of Species
This application contains claims directed to more than one species of the generic invention. These species are deemed to lack unity of invention because they are not so linked as to form a single general inventive concept under PCT Rule 13.1.
The species are as follows: the species are too numerous to list here individually but include species of Formula (I) (e.g., those disclosed in claim 20) and species of cancer (e.g., those disclosed in claim 26).
Applicant is required to elect a single disclosed compound of Formula (I) by election of every variable at a level that defines a single compound. For example, Applicant may elect a species disclosed in claim 20.
Applicant is further required to elect a single disclosed species of cancer, such as from those disclosed in claim 26 (e.g., small cell lung cancer). If Applicant elects a subgenus of cancer, such as lung cancer as disclosed in claim 25, Applicant is required to elect a species thereof (e.g., small cell lung cancer).
Applicant is required, in reply to this action, to elect a single species to which the claims shall be restricted if no generic claim is finally held to be allowable. The reply must also identify the claims readable on the elected species, including any claims subsequently added. An argument that a claim is allowable or that all claims are generic is considered non-responsive unless accompanied by an election.
Upon the allowance of a generic claim, applicant will be entitled to consideration of claims to additional species which are written in dependent form or otherwise require all the limitations of an allowed generic claim. Currently, the following claim(s) are generic: all claims.
The groups of inventions listed above do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons:
Where a single claim defines alternatives of a Markush group, the requirement of a technical interrelationship and the same or corresponding special technical features as defined in Rule 13.2, is considered met when the alternatives are of a similar nature. When the Markush grouping is for alternatives of chemical compounds, the alternatives are regarded as being of a similar nature where the following criteria are fulfilled:
(A) all alternatives have a common property or activity; AND
(B)(1) a common structure is present, that is, a significant structural element is shared by all of the alternatives; OR
(B)(2) in cases where the common structure cannot be the unifying criteria, all alternatives belong to a recognized class of chemical compounds in the art to which the invention pertains.
The phrase “significant structural element is shared by all of the alternatives” refers to cases where the compounds share a common chemical structure which occupies a large portion of their structures, or in case the compounds have in common only a small portion of their structures, the commonly shared structure constitutes a structurally distinctive portion in view of existing prior art, and the common structure is essential to the common property or activity.
The phrase “recognized class of chemical compounds” means that there is an expectation from the knowledge in the art that members of the class will behave in the same way in the context of the claimed invention, i.e. each member could be substituted one for the other, with the expectation that the same intended result would be achieved.
The chemical compounds of Formula (I) are not regarded as being of similar nature because: (1) the alternatives do not all share a common structure and (2) the alternatives do not all belong to a recognized class of chemical compounds. For example, a species A
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structurally differs to a species B
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as shown by the annotations. Specifically, R1, R2, ring A, and R3 differ greatly in chemical structure and n differs in number (1 vs. 2). Due to these structural differences, notable differences in other characteristics, i.e, utility, bioavailability, and potency, etc. would be expected between species. The artisan could not substitute one compound, above, for another and expect the same chemical behavior/function given the structural distinctions. Therefore, the alternatives do not all belong to a recognized class of chemical compounds.
The species of cancer do not all share a common etiology and respond the same way, if at all, to the same treatment modality. For example, small cell lung cancer has a different etiology from acute myeloid leukemia. These cancers will not respond the same way (be treated) to the same treatment modality. Therefore, the alternative species of cancer do not all belong to a recognized class of diseases.
During a telephone conversation with Applicant’s Representative on 02/04/2026 a provisional election was made without traverse to prosecute the species of Formula (I) that is compound 006 (dgy-12-161) (Pg. 31 Ex. 1 of the specification) and the species of cancer that is cholangiocarcinoma, claims 1-5, 8-10, 12, 14-26, and 29. Affirmation of this election must be made by applicant in replying to this Office action. Claims 6-7, 11, and 13 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected species.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
A search for the elected species compound 006:
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retrieved prior art (see SEARCH 6 of the attached search notes). Thus, the Markush search will not be unnecessarily extended in this action.
Priority
The effective filing date is 06/30/2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 12/07/2023 and 05/05/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Specification
Applicant is reminded of the proper content of an abstract of the disclosure.
In chemical patent abstracts for compounds or compositions, the general nature of the compound or composition should be given as well as its use, e.g., “The compounds are of the class of alkyl benzene sulfonyl ureas, useful as oral anti-diabetics.” Exemplification of a species could be illustrative of members of the class. For processes, the type of reaction, reagents and process conditions should be stated, generally illustrated by a single example unless variations are necessary.
In the instant case, the abstract fails to disclose the general nature of the compounds (e.g., class of diazabicyclooctyl quinazolines). Please amend to include such information.
Claim Objections
Claim 20 is objected to because of the following informalities: the recited structures are not separated with the appropriate punctuation. Please place a comma after each structure (minus the last structure) and please put the word “and” before the final structure. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 19 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 19 recites the limitation "
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". There is insufficient antecedent basis for this limitation in the claim. Specifically, the optional moieties of halo, C1-4 alkyl, or N(C1-4alkyl)2 are not all supported as substituents on each of the recited cycles. Aside from H, the R2 moieties are understood as follows:
1) O-CH2-hexahydro-1H-pyrrolizine: R2 is the C1 alkoxy O-CH2 substituted with one R6 which is hexahydro-1H-pyrrolizine;
2) O-CH2-pyrrolidine: R2 is the C1 alkoxy O-CH2 substituted with one R6 which is pyrrolidine;
3) azetidine: R2 is the 4-membered heterocycloalkyl azetidine, no R6 is specified;
4) N(H)-CH2CH2-imidazole: R2 is the NH(C2alkyl) N(H)-CH2CH2 substituted with one R6 which is imidazole;
5) O-CH2-imidazo(1,2-a)pyridine: R2 is the C1 alkoxy O-CH2 substituted with one R6 which is imidazo(1,2-a)pyridine; and
6) 1,6-diazaspiro[3.3]heptane: R2 is the 7-membered heterocycloalkyl 1,6-diazaspiro[3.3]heptane, no R6 is specified.
The cycles which are R2 are azetidine and 1,6-diazaspiro[3.3]heptane, according to parent claim 1 R2 may be substituted with 1-2 R6 including C1-4 alkyl and N(C1-4alkyl) but not halo. Thus, these R2 moieties may not be directly substituted by halo.
The cycles which are R6 are pyrrolizine, pyrrolidine, imidazole, and imidazo(1,2-a)pyridine, according to parent claim 1 R6 may be further substituted with moieties including halo and C1-6 alkyl but not N(C1-4alkyl). Thus, these R6 moieties may not be directly substituted by N(C1-4alkyl).
Thus, the optional substituents recited in claim 19 do not exactly line up with those that are allowed on R2 and R6 as defined in parent claim 1. Therefore, the metes and bounds of the claim are undefined rendering the claim indefinite.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 19 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 19 recites limitations on R2, see ¶15 above. Based on the limitations of parent claim 1: 1) the R2 moieties azetidine and 1,6-diazaspiro[3.3]heptane may not be directly substituted by halo and 2) the R6 moieties pyrrolizine, pyrrolidine, imidazole, and imidazo(1,2-a)pyridine may not be directly substituted by N(C1-4alkyl). Since claim 19 embraces embodiments wherein R2 and R6 are substituted by the forbidden moiety, claim 19 is broader in scope than parent claim 1 and does not properly further limit claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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)(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 1-5, 8-10, 12, 14-26, and 29 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by ZHANG (WO 2022/068921, pub. 04/07/2022, effectively filed 09/30/2020) evidenced by HWANG (Hwang, K., Howell, C. (2020). Bile Duct Cancer. In D. S. Hiam (Ed.), The Gale Encyclopedia of Cancer: A Guide to Cancer and Its Treatments (5th ed.)).
A machine translation of ZHANG is provided and is cited below for text; the original document is cited for figures/structures. The priority document for ZHANG is cited below as “PD”.
Regarding claims 1-5, 8-10, 12, and 14-20, ZHANG teaches the compound 6a (Pg. 222 compound 6a; PD Pg. 68 compound 6a) which is the same as the instant compound 006/dgy-12-161:
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vs.
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. The wiggly bond in the naphthyl of compound 6a is understood as equivalent to the flat bond at the corresponding location on the instant compound 006 since both represent unknown/unspecified stereochemistry. The compound 006 teaches wherein ring A is C6 aryl phenyl, R1 is H, R2 is 4-membered heterocycloalkyl substituted with 1 R6 which is N(C1alkyl)2, R3 is OH, R4 and R5 are halo (Cl and F respectively), and n is 1.
Regarding claim 21, ZHANG teaches a pharmaceutical composition comprising the compound of the invention (i.e., 6a) and one or more pharmaceutical excipients (Pg. 201 claim 19; PD Pg. 35 claim 14). Examiner understands excipient to read on the instant carrier.
Regarding claim 22-26 and 29, ZHANG teaches the compounds of the invention inhibit KRAS G12D (Pg. 208 ¶9; PD Pg. 2 Lines 5-7). ZHANG teaches a method of treating cancer mediated by KRAS G12D mutation comprising administering to a patient a therapeutically effective amount of the compound 6a (Pg. 528 ¶1225; PD Pg. 38 ¶3). ZHANG teaches the cancer is bile duct cancer (Pg. 531 ¶1232; PD Pg. 38 last ¶). Bile duct cancer is understood to be another name for cholangiocarcinoma, as evidenced by HWANG (Pg. 1 Definition Line 1).
Thus, ZHANG teaches a method of inhibiting KRAS G12D and treating cholangiocarcinoma having a KRAS G12D mutation in a subject by administering a therapeutically effective amount of the instant compound.
Claims 1-5, 8-10, 14-26, and 29 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by DAI (WO 2022/002102, pub. 01/06/2022, effectively filed 06/30/2020; cited in IDS of 05/05/2025). The priority document for DAI is cited below as “PD”.
Note: This reference was retrieved incidental to the search for the elected species and it applied here in favor of expediting prosecution. This does not indicate that the entire scope of the claims has been searched and examined.
Regarding claims 1-5, 8-10, and 14-20, DAI teaches compound 33:
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(Pg. 48 Table A compound 33; PD Pg. 38 compound 33) wherein ring A is C6 aryl phenyl, R1 is H, R2 is C1 alkoxy O-CH2 substituted with 1 R6 which is the 8-membered heterocycloalkyl hexahydro-1H-pyrrolizine, R3 is OH, R4 and R5 are halo (Cl and F respectively), and n is 1. The compound 33 matches the first compound recited in instant claim 20.
Note: instant claim 11 would be anticipated by DAI’s compound 33, above, if not withdrawn.
Regarding claim 21, DAI teaches a pharmaceutical composition comprising a compound of Table A (i.e., compound 33) and a pharmaceutically acceptable carrier (Pg. 59 ¶101; PD Pg. 43-44 ¶91).
Regarding claim 22-26 and 29, DAI teaches a method of inhibiting KRAS G12D in a cancer cell by contacting the cell with a compound of Table A (i.e., compound 33) (Pg. 63 ¶113; PD Pg. 47-48 ¶103). DAI teaches a method of treating cancer in a subject comprising administering to the subject a therapeutically effective amount of a compound in Table A (i.e., compound 33) wherein the cancer is cholangiocarcinoma and has a KRAS G12D mutation (Pg. 64 ¶115; PD Pg. 48 ¶105). DAI teaches the compound 33 inhibits KRAS G12D (Pg. 154 ¶405 Table 2; PD Pg. 114 ¶302 Table 2).
Thus, DAI teaches a method of inhibiting KRAS G12D and treating cholangiocarcinoma having a KRAS G12D mutation in a subject by administering a therapeutically effective amount of the instant compound.
Conclusion
Claims 1-5, 8-10, 12, 14-26, and 29 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARA ELIZABETH BELL whose telephone number is (703)756-5372. The examiner can normally be reached Monday-Friday 9:00-5:30.
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/S.E.B./Examiner, Art Unit 1625
/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625