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 .
Election/Restrictions
Applicant’s election without traverse of a compound of formula (I) in which examined variable R6 is naphthyl in the reply filed on 2025 October 16 is acknowledged. Claims 1-7 and 9-36 are pending. A search of the application is extended to compounds of formula (I) in which piperazine or 3,8‐diazabicyclo[3.2.1]octane ring is attached to a bicyclic ring of formula (I) in which at least one of variables X and Y is N and variable R6 is naphthalene or phenyl. Claims 1, 2, 4, 5, 7, 9, 11-13, 15-22, 24, 25, and 27-35 are examined with respect to the search scope recited above.
Claims 3, 6, 10, 14, and 23, 26, and 36 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 2025 October 16.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 2023 May 24, 2023 October 3, and 2024 November 19 were submitted in compliance and have been considered with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claim 35 is objected to because of the following informalities: the phrase “(e.g., a KRas G12D-associated cancer)” is extraneous because it merely repeats the idea stated right before it, “the cancer is associated with a KRas G12D mutation”. Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 35 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a mental calculation without significantly more. The claim(s) recite(s) a method of determining if a cancer has a KRas G12D mutation and then administering a therapeutically effective amount of a compound of claim 1. This judicial exception is not integrated into a practical application because the determination if a cancer has KRas G12D mutation can result in a cancer not having a KRas G12D mutation. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims is drawn to a mental step of determining if the cancer has a KRas G12D mutation. If the cancer does not have a KRas G12D mutation, there is no active step in the claim.
Claim Rejections - 35 USC § 112
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 29-35 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification is enabling for treatment of pancreatic ductal adenocarcinoma, colon adenocarcinoma, acute myeloid leukemia, melanoma, lung adenocarcinoma, endometrium carcinoma, and bladder carcinoma and non-enabling for the treatment of the scope of cancers recited in claims 30-35. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
The factors to be considered in determining whether a disclosure meets the enablement requirements of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 858 F.2d 731, 8 USPQ2d 1400 (Fed. Cir., 1988). The court in Wands states, “Enablement is not precluded by the necessity for some experimentation, such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is ‘undue’, not ‘experimentation’” (Wands, 8 USPQ2sd 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations” (Wands, 8 USPQ2d 1404). Among these factors are: (1) the nature of the invention; (2) the breadth of the claims; (3) the state of the prior art; (4) the predictability or unpredictability of the art; (5) the relative skill of those in the art; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
Consideration of the relevant factors sufficient to establish a prima facie case for lack of enablement is set forth herein below:
The nature of the invention and (2) the breadth of the claims:
The claims are drawn to treating cancer with a compound of formula (I) In a compound of formula (I), a piperazine ring which can be part of a bigger ring system is attached to a bicyclic ring system that contains 2-3 nitrogen ring atoms which is further substituted by another ring, system selected from phenyl, naphthyl, or indazole. Thus, the claims taken together with the specification imply a compound of formula (I) can treat cancer.
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The state of the prior art and (4) the predictability or unpredictability of the art:
LI (Nature Reviews, 2018, 18, 767-777) describes the following teachings: KRAS G12D is present in pancreatic ductal adenocarcinoma, colon adenocarcinoma, acute myeloid leukemia, melanoma, lung adenocarcinoma, endometrium carcinoma, and bladder carcinoma; and therapeutic challenges are present when studying how RAS is related to tumorigenesis (page 773, column 1, paragraph 3 to page 774, column 3, paragraph 2).
The relative skill of those in the art:
While the artisan generally would have an advanced degree in cancers related to KRAS G12D, their high level of skill and knowledge is insufficient to overcome the lack of understanding as to how what specific cancers KRAS G12D is related to.
The amount of direction or guidance presented and the presence or absence of working examples:
The specification has provided guidance for treatment of pancreatic ductal adenocarcinoma, colon adenocarcinoma, acute myeloid leukemia, melanoma, lung adenocarcinoma, endometrium carcinoma, and bladder carcinoma . Tables 1 and 2 (page 93, paragraph [0249] to page 96, paragraph [0257] describe in vitro testing.
The specification does not provide guidance for the treatment of the scope of cancers recited in claims 30-35.
The quantity of experimentation necessary:
Considering the state of the art as discussed by the references above, particularly with regards to treating cancer with a compound of formula (I) and the high unpredictability in the art as evidenced therein, and the lack of guidance provided in the specification, one of ordinary skill in the art would be burdened with undue experimentation to practice the invention commensurate in the scope of the claims.
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.
Claims 30 and 31 are 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
In the present instance, claim 30 recites the broad recitation numerous broad limitations of different categories of cancer and narrower examples of each broad category. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. For example, cardiac cancer is recited and sarcoma, myzoma, rhabdomyoma, fibroma, lipoma, and teratoma are listed too. After sarcoma, the text included in parentheses is interpreted as “such as” language. These claims are unclear because of the different scopes, the broadest scopes and the narrower scopes. More broad types of cancer are recited in claims 30 and 31: lung, gastrointestinal, genitourinary tract, liver, biliary tract, nervous system, gynecological, hematologic, and adrenal glands.
Regarding claim 35, the phrase "e.g." renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. The text following “e.g.” does not limit the cancer in the claim to a KRas G12D mutation only. See MPEP § 2173.05(d).
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.
Claim(s) 1, 2, 4, 5, 7, 13, 15, 22, and 24 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by MARX (US 20190270743, published 2019 September 5). Marx describes the intermediate compounds (page 81, column 1; page 82, column 1; page 83, column 2; page 84, column 2; page 85, column 2; page 87, column 1; page 88, column 1; page 89, column 1; page 90, column 1; page 91, column 1; page 92, column 1l; page 93, column 1; page 94, column 2; page 95, column 2; page 96 column 2; page 98, column 2; page 100, column 1; page 101, column 1; page 102, column 1; page 104, column 1; page 105, column 2; page 111, column 1;page 112, column 2; page 166, column 2; page 168, column 2; page 205, column 1; page 206, paragraph [0901]; page 207, paragraph [0908]; page 208, column 1) in which the following examined definitions apply: R3 is H; one of R2 is CH2-CN and the remaining instances of R2 are H; R1 is substituted pyrrolidine or hexahydro‐1H‐pyrrolizine; R4, R5, and R7 are each H; X is CH; Y is N; and R6 is selected from the group consisting of 2,3-dimethylphenyl, naphthyl, [chloro, methyl, or fluoro and chloro]-substituted naphthalene. Several of the compounds are shown below.
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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, 2. 4, 5, 9, 11, 13, 15, 24, 27-32, and 35 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 20-24 of copending Application No. 18/027300 (reference application); US PGPub 20230357277, rejection based on 2025 September 30 claim set. Although the claims at issue are not identical, they are not patentably distinct from each other because the compounds of claim 20 below are encompassed by the specified claims of the examined application for the following reasons: R3 and R2 are H; R1 is substituted hexahydro‐1H‐pyrrolizine; R4, R5, and R7 are each H; X is CH; Y is N; and R6 is selected from the group consisting of a substituted naphthyl or phenyl group. Claims 21-24 of 18027300 are drawn to a pharmaceutical composition and a method of treating cancer with the same compounds.
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This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 29-35 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 20-40 of copending Application No. 18644056 (reference application; US PGPub 20240309020; rejection based on 2025 June 2 claim set). Although the claims at issue are not identical, they are not patentably distinct from each other because methods of treating non-small cell lung cancer, colorectal cancer, and pancreatic cancer are done with the compound shown below. In this compound the following definitions apply: R3 and R2 are H; R1 is substituted hexahydro‐1H‐pyrrolizine; R4, R5, and R7 are each H; X is CH; Y is N; and R6 is selected from the group consisting of a substituted naphthyl group.
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This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Allowable Subject Matter
Claims 1, 2, 4, 5, 7, 9, 11, 13, 15, 22, 24, and 29-35 are not allowed.
Claims 12, 16-21, and 25 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims with respect to the scope of what has been searched.
The following is a statement of reasons for the indication of allowable subject matter: MARX (US 20190270743, published 2019 September 5) does not describe compounds in which two instances of examined variable R2 form a 3,8‐diazabicyclo[3.2.1]octane ring is attached to a bicyclic ring of formula (I) in which one instance X or Y is N. Hence the elected species appears free of the prior art of record.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NOBLE E JARRELL whose telephone number is (571)272-9077. The examiner can normally be reached 9:00 AM to 5:00 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Fereydoun Sajjadi can be reached at 571-272-3311. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/NOBLE E JARRELL/Primary Examiner, Art Unit 1699
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