DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Claims 20-50 are pending in the application.
This action is in response to applicants' amendment dated September 5, 2025. Claims 49 and 50 are newly added.
Response to Amendment
Applicant's arguments filed September 5, 2025 have been fully considered with the following effect:
This application contains claims 20-44 drawn to an invention nonelected without traverse in the reply filed on December 16, 2025. A complete reply to the final rejection must include cancellation of nonelected claims or other appropriate action (37 CFR 1.144) See MPEP § 821.01.
With regards to the 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph rejection, labeled paragraph 3) in the last office action, the applicant’s remarks have been fully considered but they are not persuasive. The applicants stated that the drug of the prodrug has an amine functional group and the drug-dienophile conjugate includes a trans-cyclooctene ring moiety where the drug is conjugated to the carbon atom adjacent to the double bond of the cyclooctene ring via a carbamate bond that includes the amine functional group. The specification describes the following examples for the drug-dienophile conjugate, page 69 (E)-cyclooctene doxorubicin prodrug (38) and page 70 (E)-cyclooctene doxorubicin prodrug (46). The applicants also stated that they have demonstrated the successful in vivo release of at least doxorubicin, auristatin MMAE, vancomycin, daptomycin, luciferase and the phospho-lyase enzyme, OspF. However, first the specification describes the prodrug which includes the drug auristatin MMAE is an antibody-drug conjugate as set forth on pages 101, 102, 113, 123 are not bound to the cyclooctene ring via a carbamate bond that includes the amine functional group. Second the specification does not describe the successful in vivo release of vancomycin, daptomycin, luciferase and the phospho-lyase enzyme, OspF and recent journal article Czuban et al., sited by the applicants in their remarks if facts teaches that the TCO-Dapto in fact has poor aqueous solubility which limits its in vivo testing.
The applicants further point to the portion of the claim where the only relevant aspect of the drug moiety is the amine functional group (which is required by the instant claims), and release will occur regardless of the other aspects of the drug. Applicants further site several references published after the priority date to support the enablement of the claimed methods which is not on point because the enablement of the claimed invention must be up to the filing date of the claims, i.e., 2011. However, many of the drugs mentioned in claim 47 have multiple amine functional groups. Prodrug means a pharmacologically inactive form of a compound which must be metabolized in vivo by a subject after administration into a pharmacologically active form of the compound in order to produce the desired pharmacological effect. The drug-dienophile conjugate is of indeterminate scope in that they vary widely from drug to drug. It is not known which drug-dienophile conjugate would form the basis for the pro-drug. The drug-dienophile conjugate wherein the pro-drugs are not described in the disclosure in such a way the one of ordinary skill in the art would know how to prepare the various compounds suggested by claims 45-47 and 49. In view of the lack of direction provided in the specification regarding starting materials, the lack of working examples, and the general unpredictability of chemical reactions, it would take an undue amount of experimentation for one skilled in the art to make the claimed compounds and therefore practice the invention.
Additionally, any drug that may be discovered in the future would be embraced by the use of drug-dienophile conjugate in the claims and would thus preempt the effort of others.
Claims 45-49 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a drug-dienophile conjugate 38, does not reasonably provide enablement for any and all drug-dienophile conjugates wherein the dienophile is other than cyclooctene and the drug is other than doxorubicin. 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 use the invention commensurate in scope with these claims, for reasons of record and stated above.
With regards to the 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph rejections, labeled paragraph 4a) of the last office action, the applicant’s amendments and remarks have been fully considered but they are not persuasive.
a) The applicants’ stated that those of ordinary skill would understand the meaning and scope of a derivative of the drugs listed in claim 47 and that the functional requirement for a drug of the conjugate to work in the instant methods is that the drug has an amine functional group (as explained above the instant claims only require that the drug is part of a conjugate and is released upon contact with a tetrazine—the drug does not need to have any particular biological activity). However, while the drugs are conjugated through the amine functional group that still leaves a magnitude of possible combinations that would be embraced by “derivative” of which are neither supported nor contemplated.
Claim 47 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 applicant regards as the invention, for reasons of record and stated above.
With regards to the provisional nonstatutory double patenting rejections the Applicants have requested that each be held in abeyance until there is allowable subject matter. The following provisional nonstatutory double patenting rejections are herein maintained for reasons of record.
Claims 45-48 and newly added claims 49-50 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of copending Application No. 17/052,927 (reference application).
Claims 45-48 and newly added claims 49-50 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 21 of copending Application No. 17/052,925 (reference application).
Claims 45-48 and newly added claims 49-50 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 20-43 of copending Application No. 17/619,796 (reference application).
Claims 45-48 and newly added claims 49-50 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9-11, 15 and 30-33 of copending Application No. 17/619,794 (reference application).
Claims 45-48 and newly added claims 49-50 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 5-8, 11, 12, 17, 18 and 31-33 of copending Application No. 17/619,791 (reference application).
With regards to the nonstatutory double patenting rejections the Applicants have requested that each be held in abeyance until there is allowable subject matter. The following nonstatutory double patenting rejections are herein maintained for reasons of record.
Claims 45-48 and newly added claims 49-50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 9,421,274.
Claims 45-48 and newly added claims 49-50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 9,463,256.
Claims 45-48 and newly added claims 49-50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 9,427,482.
Claims 45-48 and newly added claims 49-50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 9,913,921.
Claims 45-48 and newly added claims 49-50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-27 of U.S. Patent No. 9,931,408.
Claims 45-48 and newly added claims 49-50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 10,004,810.
Claims 45-48 and newly added claims 49-50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 10,376,594.
Claims 45-48 and newly added claims 49-50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 10,927,139.
Claims 45-48 and newly added claims 49-50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 20-34 of U.S. Patent No. 10,967,069.
Claims 45-48 and newly added claims 49-50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-41 of U.S. Patent No. 11,617,799.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRENDA L COLEMAN whose telephone number is (571)272-0665. The examiner can normally be reached Mon-Fri 10-6 (flex).
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/BRENDA L COLEMAN/Primary Examiner, Art Unit 1624
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