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
Election/Restrictions and Status of the Claims
Applicant’s election without traverse of Group I, comprising claims 1-8, 10-11, and 20, as well as the conjugate I-1 as the single small molecule conjugate in the response filed on April 11th 2026 is acknowledged. Claims 1-20 are pending. Claims 9 and 12-19 are withdrawn from further consideration as being directed towards a nonelected group until a generic claim has been found allowable. Claims 1-8, 10-11, and 20 are examined on their merits.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The Information Disclosure Statement filed on March 13th 2023 is in compliance with the provisions of 37 CFR 1.97 and has been considered in full. A signed copy of references cited from the IDS is included with this Office Action.
Claim Interpretation
Claim 1 recites “A small-molecule conjugate…, wherein a structure of the small- molecule conjugate is shown…” For the purpose of examination, the “a” will be interpreted as “the.”
Similarly, claim 6 recites, “wherein an A-B is selected from one of the following structures…” For the purpose of examination, the phrase will be read as “wherein A-B is selected from one of the following structures…”
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.
Claims 1, 3, 4, 5, 20, and their dependent claims, 2, 6, 10, and 11 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.
Claims 1, 4, 5 are indefinite for the phrases, “a derivative thereof,” “an analogue thereof,” and “a combination thereof,” because one of ordinary skill in the art could not reasonably determine the metes and bounds of the claim from the claim language. The three terms are unclear, because one of ordinary skill in the art could not reasonably determine the entire scope of compounds encompassed by the term, which is not defined in the specification, but only repeated in the same context (specification, pg. 2-5).
Claim 1 is indefinite for the Markush group defining the ‘A’ moiety, because it is unclear which functional groups preside within the definition of ‘A.’ The repeated usage of the ‘and’ and ‘or’ terms within the definition of ‘A’ makes the scope of the moiety unclear, as one of ordinary skill in the art could not clearly distinguish which substituents are in the ‘A’ group and which are not. Appropriate correction to provide a clear definition of the group encompassed by the chemical moiety, “A,” is required.
Regarding claims 3 and 20, the phrase "may be linked" renders the claims indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. 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.
Claims 1-4, 6, 10-11, 20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Crew (US 2017/0008904 A1 published on January 12th 2017).
The claims are directed towards small-molecule conjugates comprising the MDM2-binding moiety idasanutlin, as shown below:
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Crew teaches the compound,
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Crew’s compound comprises the same idasanutlin moiety, connected to a linker spacing group, an amide bond, and a JQ1 drug moiety,
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Crew thereby anticipates the compound of claim 1.
Claim 2 limits the B moiety to be selected from a group that includes an amide bond. Crew thereby anticipates claim 2 for the same reasons as claim 1.
Claim 3 limits the drug moiety in claim 1 to chemotherapeutic drugs. As the JQ1 moiety of Crew is known to treat various cancers1, it is encompassed as a “chemotherapeutic drug,” and Crew anticipates claim 3.
Claim 10 is directed towards a pharmaceutical composition comprising the molecule of claim 1 and at least one therapeutic agent. Crew teaches such a composition (Crew, pg. 96, claim 25), anticipating claim 10.
Claim 11 is directed towards a pharmaceutical composition comprising the molecule of claim 1, and is anticipated by Crew for the same reasons as claim 10.
Claim 20 requires that the drug moiety of claim 10 is a chemotherapeutic drug and is anticipated by Crew for the same reasons as claims 3 and 10.
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.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Crew in view of Howard (WO 2011/130598 A1 published on October 20th 2011).
Claim 6 limits the compound of claim 2 to require that the A-B moiety combination is selected from a group that includes
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For the teachings of Crew as they are relevant to claim 2, see the above 102 rejection for claim 2. Regarding the A-B linker, while Crew does not explicitly teach such a linker, one of ordinary skill in the art would have had a reasonable expectation of success in linking the two drugs in Crew’s conjugates using such a linker, because such a linker is already known in the art to be used in anticancer conjugates. For example, see Howard, who teaches the compound,
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which includes such a linker.
As a conjugate comprising such a linker is obvious, claim 6 is prima facie obvious.
Allowable Subject Matter
Claims 4-5 and 7-8 are free of the prior art.
Applicant has developed small-molecule conjugates comprising the MDM2-binding moiety idasanutlin, as shown below:
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Conjugates comprising such an idasanutlin moiety are numerous in the art. However, in every case, the MDM2 inhibitor is either used as a moiety to target other proteins for degradation, or used in combination with a ubiquitin ligase inhibitor to target the MDM2 for degradation (WO2013178570 A1) (WO2017176957 A1) (WO2019195609 A2) (WO2021188948 A1) (WO2018119357 A1) (WO2022261220 A1).
Applicant’s invention is unique in that the MDM2 inhibitor is used as a delivery mechanism for additional chemotherapeutic drugs. As such, applicant’s compounds comprising the specific chemotherapeutic drugs described are novel and nonobvious.
Claims 4-5 and 7-8 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Anthony Seitz whose telephone number is (703)756-4657. The examiner can normally be reached 7:30 AM ET - 5:00 PM ET M-F.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Lundgren can be reached at (571)272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ANTHONY JOSEPH SEITZ/Examiner, Art Unit 1629
1 For evidentiary support, see Belkina (Belkina et al., BET domain co-regulators in obesity, inflammation and cancer. Nat Rev Cancer. 2012 Jun 22;12(7):465-77)
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