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 .
Status of Claims
The amendments to the claims filed April 4, 2024 are acknowledged and entered. Claims 1-15, 17, 19-21 and 24-25 are pending.
Priority
This application is a 371 of PCT/US2022/077376, filed September 30, 2022, which claims the benefit of 63/252,227, filed October 5, 2021.
Information Disclosure Statement
Acknowledgement is made of the Information Disclosure Statement filed on May 20, 2024. All references have been considered except where marked with a strikethrough.
Specification
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any of the errors of which applicant may become aware of in the specification.
Claim Rejections - 35 USC § 112b
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 17 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 17 recites the limitation "a second base" which renders the claim indefinite because claim 17 depends from claim 1 which does not recite a first base. No base is recited in claim 1 and therefore the claim could be amended to recite “a base”.
Claim Rejections - 35 USC § 103
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.
Claims 1-15, 17, 19 and 24-25 are rejected under 35 U.S.C. 103 as being unpatentable over Rogers et al. (WO2019/126121, published June 27, 2019)(hereinafter “Rogers”).
Rogers teaches macrocyclic compounds of generic formula (I) (see paragraph [005]), including the claimed compound of Formula (I) (see claim 42) that are useful for the treatment of cancer (Abstract and claim 44). Rogers discloses that the generic compounds of formula (I) which includes the compound of Formula (I) of the claims may be prepared by a variety of general synthetic methods (e.g. see General Method D at [0301]; General Method E at [0307] and General Method I at [0334]). Rogers explicitly states
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Rogers illustrates the compound of Formula (I) of the claims can be prepared by General Method E ([0307]); however, with regard to instant claims 1-8, Rogers also teaches a generic compound of formula (I), which includes the compound of Formula (I) of the claims, may be prepared by General Method I ([0334]; pictured below illustrating an example synthesis of compound 7). General Method I teaches the synthesis of compounds of formula (I) starting from intermediates beginning with C and D (see e.g. C-1 and D-2 below).
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Rogers further teaches intermediate C-1 (pictured above and below; also on page 79) which corresponds to a compound of instant Formula (III) wherein X2 is ethyl, and intermediate D-2 (page 82; pictured below; Note: compound D-1 appears to be mislabeled D-2 in the scheme above, see page 82 and product 7) which corresponds to a compound of instant Formula (II) wherein Y1 is methansulfonate (OMs) and X1 is tert-butylcarbonyl (Boc). A person of ordinary skill in the art would easily recognize that a compound of instant Formula (IV) is the product formed by combining intermediates C-1 and D-2 listed at pages 79 and 82 (also pictured below) according to General Method I, and moreover that completion of General Method I starting from intermediates C-1 and D-2 produces the compound of instant Formula (I). The person of ordinary skill in the art would understand that treatment of the product formed from C-1 and D-2 (i.e. the compound of Formula (IV)) with the first two steps of the reaction sequence
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produces the compound instant Formula (V) which is then cyclized in the third step to produce the compound of instant Formula (I).
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Regarding claims 9-11, Rogers teaches the method comprises a base (see General Method I; both Cs2CO3 and LiOH are inorganic bases).
Regarding claims 12-13, Rogers teaches the intermediates corresponding to Formula (II) and Formula (III) are combined in DMF at room temperature (see General Method I above, combination of C-1 and D-2; see [0336]). Room temperature could be understood to mean 20-25 ⁰C which falls within the claimed range of about 10 ⁰C to about 30 ⁰C.
Regarding claims 14-15, Rogers teaches wherein the cyclizing comprises pentafluorophenyl diphenylphosphinate (FDPP) and wherein the solvent for cyclizing is dichloromethane (DCM) (see General Method I, step
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).
Regarding claim 17, the instant compounds of Formula (VI) and Formula (V) would be the result of practicing the synthesis of Formula (I) according to General Method I starting with intermediates C-1 and D-2 disclosed by Rogers (see General Method I, steps
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).
Regarding claims 19 and 24-25, synthesis of the prior art compound corresponding to instant Formula (I) according to General Method I would involve cyclizing a compound of instant Formula (VI). The broadest reasonable interpretation of “oxygen protecting group” in view of the specification would be a hydrogen atom (see definition at [0022] of the specification) which masks the reactivity of oxygen. General Method I thus would involve the compound of Formula (VI). Moreover, in practicing General Method I starting from compounds C-1 and D-2 one would have possessed the compound of Formula (VI) as set forth in claims 24-25 (see General Method I, step
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)
The difference between the prior art and the instant claims is that the instant claims are drawn to producing a compound of Formula (I) by General Method I and the instant claims explicitly recite intermediate compounds formed (e.g. Formula (V)) during the process. The reference does not explicitly recite a synthesis of instant Formula (I) by General Method I; however, it would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the instant application to prepare instant Formula (I) according to the prior art method General Method I as is claimed because the reference disclosed that General Method I could be used to make the compound of instant Formula (I). Moreover, the compounds of instant Formulae (II) and (III) required to prepare instant Formula (I) according to General Method I were already disclosed by Rogers. It would have been obvious to combine these intermediates according to General Method I to produce instant Formula (I) as is claimed.
One would have been motivated as a matter preparing instant Formula (I) for use in treating cancer. Further, one would have been motivated to use General Method I as a routine matter of exploring alternative synthetic routes disclosed by the reference to determine which is superior for preparing the compound.
One would have had a reasonable expectation of success because the reference disclosed that the compound of Formula (I) could be prepared by General Method I and the intermediates required to practice General Method I in the synthesis of Formula (I) had specifically been disclosed.
Claim(s) 19-21 are rejected under 35 U.S.C. 103 as being unpatentable over Rogers et al. (WO2019/126121, published June 27, 2019)(hereinafter “Rogers”) as applied to claim 19 above, and further in view of Wang et al. (The Journal of Organic Chemistry 2016, 81, 6672-6676).
The teachings of Rogers were discussed above and are incorporated herein by reference.
Regarding claims 20-21, Rogers teaches wherein the cyclizing comprises a base (see General Method I,
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; DIEA is an organic base). Rogers does not teach wherein cyclizing comprises the organic base 1,5,7-Triazabicyclo[4.4.0]dec-5-ene required by the claims; however, Wang teaches that 1,5,7-Triazabicyclo[4.4.0]dec-5-ene is the optimal base for a cyclization reaction (see Results and Discussion, 1,5,7-Triazabicyclo[4.4.0]dec-5-ene (TBD); see Table 1 and Table 2).
The difference between the prior art and the instant claims is that the claims require 1,5,7-Triazabicyclo[4.4.0]dec-5-ene; however, it would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the instant application to perform the cyclization reaction with 1,5,7-Triazabicyclo[4.4.0]dec-5-ene because 1,5,7-Triazabicyclo[4.4.0]dec-5-ene was an organic base that was known to be optimal for cyclization reactions.
One would have been motivated as a matter of optimizing cyclization reaction conditions in order to maximize production of the compound of Formula (I).
One would have had a reasonable expectation of success because Rogers taught the cyclization reaction required an organic base and 1,5,7-Triazabicyclo[4.4.0]dec-5-ene was an organic base known to work well in cyclization reactions.
Conclusion
No claim is allowed.
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June 12, 2026
/KEVIN S MARTIN/Examiner, Art Unit 1624
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