Detailed Action
► The applicant's Preliminary Amendment filed 29 NOV 2023 has been entered. Following the entry of the Preliminary Amendment, Claim(s) 1-18 is/are pending.
► The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . 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 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.
Sequence Rules
► This application complies with the sequence rules and the sequence(s) have been entered by the Scientific and Technical Information Center.
Priority
► This application claims foreign priority to English Language EP20207850.7 filed 16 NOV 2020. A copy of this document was provided 16 MAY 2023.
35 U.S.C. 112(b)/ 112 (pre-AIA ), second paragraph
► 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.
Claim Rejection(s) under 35 U.S.C. 112(b)
► Claim(s) 4, 15 and 17 is/are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite in that it fails to point out what is included or excluded by the claim language.
Claim 4 recites “for S.aureus” , “for coronavirus” and for “cancer cells”. It is unclear what is intended. For the evaluation of the prior art the examiner has assumed that the phrase recited above should read something like (e.g. for the treatment of S. aureus). Likewise, Claim 15 recites “for S.aureus” , “for coronavirus” and for pancreatic/breast cancer”. It is unclear what is intended. For the evaluation of the prior art the examiner has assumed that the phrase recited above should read something like and /or similar to e.g. “for the treatment of S. aureus”. Please clarify.
35 U.S.C. 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.
► 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.
Claim Rejection(s) under 35 U.S.C. 103
► Claim(s) 1-3, 5, 7-11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hsu et al. [Bioconjugate Chemistry 31:1804-1811(JUN 2020) – hereinafter “Hsu”] in view of Hernandez et al. [Nature Medicine 20(3) :301(2014) – hereinafter “Hernandez”].
Claim 1 is drawn to a composition (i.e. a drug delivery system) comprising a polynucleotide sequence susceptible to cleavage by a specific nuclease derived from a bacterium or a mammalian cell, wherein the polynucleotide sequence_ comprises an oligonucleotide sequence of RNase-resistant modified RNA bases and/or nuclease-resistant DNA bases, acting as a resistant moiety, directly-linked to ii) a polynucleotide sequence susceptible of being cleaved by a specific nuclease derived from a bacterium or a mammalian cell; wherein the polynucleotide sequence susceptible of being cleaved by a specific nuclease derived from a bacterium or a mammalian cell is in turn directly-linked to a pharmacological active ingredient, wherein the polynucleotide sequence when cleaved at the cleaving site, releases the pharmacological active ingredient.
Hsu teach a drug delivery system comprising a targeting antibody attached to an oligonucleotide linker which oligonucleotide linker is in turn directly-linked to a pharmacological active ingredient (i.e. a drug). That said, Hsu does not expressly teach the use of an oligonucleotide linker as recited by Claim 1 (i.e. an oligonucleotide having a sequence of RNase-resistant modified RNA bases and/or nuclease-resistant DNA bases, acting as a resistant moiety, directly-linked to a polynucleotide sequence susceptible to being cleaved by a specific nuclease derived from a bacterium or a mammalian. However such oligonucleotide linkers were known. Consider at least Hernandez , Table 1 and the oligo called “TT probe (FAM labelled)”. Accordingly, absent an unexpected result it would have been prima facie obvious to the PHOSITA at the time of the invention to substitute the linker of Hernandez for that of Hsu.
Please note that substitution of one known second method/reagent with known properties for a first known method/reagent with known properties would have been prima facie obvious to the ordinary artisan at the time of the invention in the absence of an unexpected result. As regards the motivation to make the substitution recited above, the motivation to combine arises from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. Support for making this obviousness rejection comes from the M.P.E.P. at 2144.07 and 2144.09, as well as, the SCOTUS decision in KSR International. Co. v. Teleflex, Inc., et al., 550 U.S.398 (2007).
Claim 3 is drawn to an embodiment of the system of Claim 1 wherein RNase-resistant modified RNA bases and/or nuclease-resistant DNA bases comprise chemically modified nucleotides.
Hernandez teach this limitation, see at least Table 1.
Claim 5 is drawn to an embodiment of the system of Claim 1 wherein drug is selected from a defined group.
Hsu teach the use of the anticancer drug “T-DM1” in their drug delivery system.
As regards Claim 7-9, see at least Table 1 in Hernandez.
As regards Claim 10-11, see at least Table 1 in Hernandez. Also note that Hernandez teach oligonucleotides by phosphoramidite chemistry, see especially the section entitled “Online Methods” which begins on 3459.
► Claim(s) 5-6 and 13, 16 and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hsu in view of Hernandez as applied above in view of Chari et al. [US 2001/0036923 – hereinafter “Chari].
Claim 5 is drawn, in part, to an embodiment of the system of Claim 1 wherein drug is selected from a defined group which includes an anthracycline. Claim 6 is drawn to an embodiment of the system of Claim 5 wherein drug is selected from a defined group which includes doxorubicin (hereinafter “DOX”).
Hsu in view of Hernandez reasonably suggest a system comprising most of the limitation as recited by Claim 5 but fail to teach a drug which is an anthracycline. However antibody-anthracycline (e.g. DOX) conjugates were known, consider at least Chari at paras 74 and 108. Accordingly, absent an unexpected result it would have been prima facie obvious to the PHOSITA at the time of the invention to substitute the drug of Chari for that of Hsu.
Please note that substitution of one known second method/reagent with known properties for a first known method/reagent with known properties would have been prima facie obvious to the ordinary artisan at the time of the invention in the absence of an unexpected result. As regards the motivation to make the substitution recited above, the motivation to combine arises from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. Support for making this obviousness rejection comes from the M.P.E.P. at 2144.07 and 2144.09, as well as, the SCOTUS decision in KSR International. Co. v. Teleflex, Inc., et al., 550 U.S.398 (2007).
Also note that the antimetabolites : floxuridine and gemcitabine were known, as were antibody drug conjugates thereof, consider at least Kunz et al.[US 2006/0002942 – hereinafter “Kunz”].
As regards Claim 13, note especially the teaching found in paras 74 and 108 of Chari, wherein DOX- antibody conjugates are disclosed.
As regards Claim(s) 16 and 18, note especially the Table 1, wherein Hernandez teach the use of 2’-O-methylnucleotides
► Claim(s) 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hsu in view of Hernandez as applied above and further in view of Zikria et al. [US 2006/0127387 – hereinafter “Zikria”] and/or Cal et al. [Exp Opinions Ther Pat. 27(2) :179-189(2017) – hereinafter “Cal”]
Claim 12 is drawn to an embodiment of the composition of Claim 1 wherein the pharmacological active ingredient (i.e. drug) is a bacteriostatic or bactericidal compound and the polynucleotide sequence is susceptible of being cleaved by a specific nuclease derived from a bacterium.
Hsu in view of Hernandez reasonably suggest a system comprising most of the limitation as recited by Claim 12 but fail to teach a drug having bacteriostatic or bactericidal activity. However antibiotic drugs (i.e. drug having bacteriostatic or bactericidal activity) were known as were antibody-drug conjugates thereof, consider at least Zikria and/or Cal. Zikria teach antibody-antibiotic conjugates (i.e. bacteriostatic or bactericidal compound – antibody conjugates), see at least para 6 . Cal teach antibody-drug conjugates for treatment of bacterial disease.
Accordingly, absent an unexpected result it would have been prima facie obvious to the PHOSITA at the time of the invention to substitute the drug of Zikria for that of Hsu in view of Hernandez. Please note that substitution of one known second method/reagent with known properties for a first known method/reagent with known properties would have been prima facie obvious to the ordinary artisan at the time of the invention in the absence of an unexpected result. As regards the motivation to make the substitution recited above, the motivation to combine arises from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. Support for making this obviousness rejection comes from the M.P.E.P. at 2144.07 and 2144.09, as well as, the SCOTUS decision in KSR International. Co. v. Teleflex, Inc., et al., 550 U.S.398 (2007).
► Claim(s) 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hsu in view of Hernandez as applied against Claim 1 and 13 above and further in view of Jo et al. [Cellular and Molecular Life Sciences [1994) – hereinafter “Jo”].
Claim 14 is drawn to an embodiment of the composition of Claim 1 wherein the pharmacological active ingredient (i.e. drug) is selected from a defined group and the
polynucleotide sequence is susceptible to cleavage by a specific nuclease derived from a mammalian cells.
Note that at least Jo teach specific nuclease(s) derived from mammals [e.g. engineered zinc -finger nuclease(s)]. Also note at least Fletcher et al. [US 2019/03090523 – hereinafter “Fletcher”] who suggest antibody- protein (i.e. zinc finger nuclease) conjugates.
► Claim(s) 4, 15 and 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hsu in view of Hernandez as applied above against Claim(s) 1 and 4 and further in view of Yang et al. [Material Science & Engineering C89:328-335(2018)- hereinafter “Yang”] and/or Yeo et al. [Scientific Reports 8:2521(2018) – hereinafter Yeo].
As regards, Claim(s) 4, 15 and 17 note that Yang teach Gemcitabine antibody conjugates for the treatment in pancreatic cancer while Yeo teach Floxuridine antibody conjugates useful for treatment of S. aureus infections.
Conclusion
C. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Ethan Whisenant whose telephone number is (571) 272-0754. The examiner can normally be reached Monday-Friday from 8:30 am -5:30 pm EST or any time via voice mail. If repeated attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Anne Gussow, can be reached at (571) 272-6047.
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EXAMINER SEARCH NOTES
20 FEB 2026 - ECW
Databases searched: All available via PE2E SEARCH
CAplus, Medline and BIOSIS via STNext; and Google Scholar (note the search terms used below)
Performed Similarity search(es) as appropriate
Reviewed the parent(s), if any, and any search(es) performed therein : see the BIB data sheet
Reviewed, the search(es), if any, performed by prior examiners including any international examiners.
Planned Search
Search terms:
All Inventor(s) e.g. Hernandez F?/au
Drug delivery system
Nuclease$
RNA or DNA or oligonucleotide$
Nuclease resistant
Antibody (oligonucleotide or drug) conjugate$
Floxuridine or Doxorubicin or gemcitabine
2’-O-methyl nucleotide$
► See the Examiner’s PE2E SEARCH notes/strategy in IFW