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 .
Priority
The present application claims priority to the applications, CN202011463704.1 and PCT/CN2021/136769, with the effective filing dates of 11 December 2020 and 9 December 2021, respectively.
Claim Status
This Office Action is in response to Applicant’s Response to Restriction Requirement filed, 5 February 2026.
Applicant’s election without traverse of Group I (claims 1-13 and 15) and Compound 48 (
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) in the reply filed on 5 February 2026 is acknowledged.
Claims 14 and 16-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group (Group II: claims 14 and 16; Group III: claims 17-18), there being no allowable generic or linking claim.
Claims 11-13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Claim 11 specifies a list of compounds: 32-1 and 65—96, which does not read on the elected species. Claim 12 specifies a list of compounds: 1-2—7-2, 8, 9-2, 10, 11-2—14-2, and 15-29, which does not read on the elected species. Claim 13 specifies a list of compounds: 1, 2-1—7-1, 9-1, 11-1—14-1, which does not read on the elected species.
Election was made without traverse in the reply filed on 5 February 2026.
Information Disclosure Statement
The Information Disclosure Statements filed on 27 May 2023, 3 Nov 2024, 27 Jan 2025, 23 June 2025, and 31 Oct 2025 and the references cited therein have been considered, unless indicated otherwise.
The reference, You (Pharm. Chem., 2004, 32-34), wherein an English abstract was not provided, is lined through.
Specification
1. The following title is suggested: “Camptothecin Derivatives, Compositions, and Uses Thereof.” The Examiner notes that “novel” will not be considered part of the invention, should not be included at the beginning of the title of the invention, and will be deleted when the Office enters the title in the Office’s computer records, and when the patent issues. See MPEP § 606.
Claim Interpretation
For clarity, the Examiner interprets the phrase “active ingredient” in claim 15 to be a compound of Formula I with biological activity.
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.
2. Claim(s) 1-10 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Xu (WO 2020/063676, published 2 Apr 2020, see IDS filed 27 May 2023, citations to English equivalent: U.S. Patent Publication 2021/0353764, published 18 Nov 2021) in view of Terasawa (EP0495432, published 29 May 1996, see IDS filed 27 May 2023) as evidenced by Surur (Arch. Chem. Life Sci., 2019, 352(e1800248), 1-11).
Xu teaches antibody drug conjugates of compound:
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(abstract).
Xu specifically teaches Compound 2-A:
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(page 17). Further, the compounds of Xu have the same stereochemistry. Flipping Compound 2-A across the y-axis and rotating counterclockwise 90° results in the following:
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.
Additionally, Compounds 48 and 2-A both have three stereocenters: cyclopropyl, ethyl, and amide. The cyclopropyl stereocenter has the following priority of substituents: (1) OH, (2) carbonyl, (3) cyclopropyl, and (4) hydrogen, resulting in assignment of (S). The ethyl stereocenter has the following priority of substituents: (1) OH, (2) carbonyl, (3) carbon of alkene, and (4) hydrogen, resulting in assignment of (S). However, the assignment of the amide stereocenter in Compound 48 differs from Compound 2-A of Xu due to differences in priority of substituents. In Compound 48 of the claimed invention, the priority of substituents is the following: (1) N of amide, (2) carbon adjacent to the sulfide, (3) carbon of alkene, and (4) hydrogen, resulting in assignment of (R). In Compound 2-A of Xu, the priority of substituents is (1) N of amide, (2) carbon of alkene, (3) carbon adjacent to methylene, and (4) hydrogen, resulting in assignment of (S). Despite their differences in substituent priority and thus amide stereochemical assignment, both compounds have the amide at the hash position and the hydrogen at the wedge position, which results in the amide of Compound 48 of the claimed invention occupying the same three-dimensional space as the amide of Compound 2-A in Xu.
Xu fails to teach compounds having a sulfide in the northern cyclohexyl ring.
Terasawa teaches camptothecin derivatives, such as Example 12:
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, which incorporate sulfides into the cyclohexyl ring for better solubility in water (page 2, lines 24-27; page 17, lines 6-25), as evidenced by Surur. Surur specifies incorporation of sulfides in drugs to improve water solubility (page 6, column 1, paragraph 2).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention to simply substitute the methylene of Compound 2-A of Xu with the sulfide of Terasawa to obtain a compound of Formula (I):
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, to arrive at instant claim 1. One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because:
-Xu teaches camptothecin derivatives, which are used in antibody-drug conjugates ([0007]),
-Xu teaches the Compound 2-A:
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,
-Xu teaches that camptothecin derivatives show anti-tumor effects via inhibiting topoisomerase I ([0007]),
-Xu teaches further development of antibody-camptothecin conjugates with better efficacy is needed ([0007]),
-Terasawa teaches camptothecin is a penta-cyclic alkaloid that exhibits anti-tumor activity from its capability of inhibiting nucleic acid synthesis (page 2, lines 11-12),
-Terasawa teaches Example 12:
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,
-Terasawa teaches discontinuation of clinical trial in the United States due to safety concerns (page 2, lines 13-14),
-Terasawa teaches previous compounds exhibited poor solubility in water and thus there is a need to synthesize camptothecin derivatives with better activity and reduced toxicity (page 2, lines 14-18),
-Terasawa teaches that opening the lactone leads to poor anti-tumor activity (page 2, lines 19-22), and
-Terasawa teaches that inclusion and derivatization of the hexacyclic ring aids in water solubility (page 2, lines 24-27).
As such, an artisan having ordinary skill in the art would have been motivated to substitute one known element (methylene) for another (sulfide) to predictably arrive at a compound of Formula (I):
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.
Regarding claim 2, Xu teaches R8 is OH (Compound 2A, page 17).
Regarding claim 3, Xu teaches R1 is a F and R2 is Me (Compound 2A, page 17).
Regarding claim 4, Xu teaches R3 is Et (Compound 2A, page 17).
Regarding claim 5, Terasawa teaches X is S (Example 12, page 17).
Regarding claim 6, Xu teaches R5 is H (Compound 2A, page 17).
Regarding claim 7, Xu teaches R6 is
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and R7 is H (Compound 2A, page 17).
Regarding claim 8, Xu teaches
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is
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(Compound 2A, page 17).
Regarding claim 9, Xu teaches R8 is OH and
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is
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(Compound 2A, page 17).
Regarding claim 10, Xu teaches
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(Compound 2A, page 17).
Regarding claim 15, Xu teaches a pharmaceutical composition of camptothecin derivatives having a pharmaceutically acceptable carrier or excipient ([0206]). Further, Xu teaches that Compound 2 (the racemate) has biological activity ([0734]).
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Madeline M Dekarske whose telephone number is (571)272-1789. The examiner can normally be reached Monday - Thursday 10am - 4pm.
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/MADELINE M. DEKARSKE/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622