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
This office action is in response to the application filed on 13 November 2023. Claims 1-2 are pending.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-2 are rejected under 35 U.S.C. 103 as being unpatentable over Xin et al. (Carbon glycoside glycosylated tetravalent platinum compound as well as synthesis method and application thereof, CN113072594A, 2021), and further in view of Ihrlund et al. (3-bromopyruvate as inhibitor of tumour cell energy metabolism and chemopotentiator of platinum drugs, Molecular Oncology 2008, 2, 94-101) and Allen et al. (Ansel’s pharmaceutical dosage forms and drug delivery systems, 10th edition, Wolters Kluwer, 2014).
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Xin discloses the oxaliplatin prodrug, as illustrated above, which differs from the claimed chemical structure of claim 1 by substitution of the 3-bromopyruvate with propyl acetate.
While Xin discloses the propyl acetate substituted oxaliplatin prodrug, they do not teach substitution of an axial 3-bromopyruvic acid ligand or an oral dosage form.
The deficiency of 3-bromopyruvic acid as a ligand is rectified by Ihrlund, who teaches that 3-bromopyruvate is a lactate analog, likely taken up in cells by lactate transporters that are overexpressed in tumor cells, inhibits hexokinase and glycolysis, induces reactive oxygen species, and induces cell death in cultured tumor cells under hypoxic conditions and in the absence of p53. Ihrlund also teaches that bromopyruvate acts as a potentiator of either cisplatin or oxaliplatin, observing necrosis induction in HCT116 cells, a human colorectal carcinoma cell line, when treated with bromo pyruvate and oxaliplatin. This therapeutic approach targeting glycolysis is salient for several types of carcinomas, including breast, kidney, liver and lung. Thus, the person of ordinary skill in the art at the time of the effective filing date of the instant application would have been motivated with a reasonable expectation of success to modify the oral Pt(IV) anti-cancer drug of Xin and substitute the axial propyl acetate ligand with an axial 3-bromopyruvate ligand to benefit from the properties of 3-bromopyruvate, which would be expected to potentiate the anti-cancer effects of the oxaliplatin taught by Xin. This ligand exchange could also potentially confer a means of active transport via lactate transporters to improve a number of pharmacokinetic properties such as permeability and bioavailability. Furthermore, increased active transport in tumor cells implies a degree of target specificity over healthy cells.
Allen overcomes the lack of oral dosage form by teaching in extensive form the nuances of drug development, including from initial small molecule search in the in vitro and in vivo phase into the clinical stage, the role drug formulation plays in each step, and very extensive guides as to how to approach formulation, including oral formulation, to achieve therapeutically relevant outcomes. As such, it would be prima facie obvious, to a person of ordinary skill in the art, to substitute the structurally similar oxaliplatin complex of the propyl acetate with bromopyruvate, given the known antineoplastic properties, increased uptake of bromopyruvate in cancer cells, the evidence of potentiation to platinum-based drugs by bromopyruvate, and the resulting combinatorial therapy arising from targeting two different cancer liabilities. Additionally, a person of ordinary skill in the art would utilize the breadth of knowledge taught by Allen to design an appropriate formulation for oral dosing to confer all the advantages of oral dosing, including but not limited to, convenience to the patient in terms of the timing of taking the dose, pain to the patient in terms of the injection process or anxiety derived from, a sense of control for the patient including effects to their work and life schedules, potentially fewer side effects with the use of oral modified-release dosage forms, all in contrast to more traditional cancer dosing means such as intravenous injection, which are often painful, inconvenient, and can induce more adverse events.
Summary
Claims 1-2 are rejected under 35 U.S.C. 103.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Allen Chao whose telephone number is (571)272-7001. The examiner can normally be reached Monday - Friday 0700-1300.
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/ALLEN CHAO/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622