DETAILED ACTION
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 the Claims
This action is in response to papers filed 05/22/2026 in which claims 12, 14, 16, and 18 were canceled; and claim 1 was amended. All the amendments have been thoroughly reviewed and entered.
As previously discussed, Applicant elected formula (1a) from claim 5:
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as the species of compound according to formula (I). The elected species reads on claims 1-2, 4-11, and 19-23.
As previously discussed, claims 3, 13, 15, 17, and 24 remained withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species and group/invention, respectively, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/21/2025.
Claims 1-2, 4-11, and 19-23 are under examination.
Withdrawn Objection/Rejections
The Examiner has re-weighted all the evidence of record. Any rejection and/or objection not specifically addressed below is hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
New Rejections
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.
Claim(s) 1, 2, 4-6, 8-11, 19, and 21-23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ruiz-Hernández et al (Polymer Chemistry, 2014, 5: 1674-1681; cited in IDS filed 01/04/2023) in view of Aben et al (US 2009/0227647 A1).
Elected species: Applicant elected formula (1a) from claim 5:
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as the species of compound according to formula (I), wherein n is 2-6.
Regarding claims 1, 2, 4-6, 10, 19, and 22-23, Ruiz-Hernández teaches doxorubicin-prodrug loaded in mPEG-b-p(HPMAmLac2-co-AzEMA) micelles (pg-micelles) having the following structure:
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(Abstract; Introduction; pages 1675-1680; Fig(s) 2-4). It is noted that Ruiz-Hernández teaches the doxorubicin-prodrug loaded within mPEG-b-p(HPMAmLac2-co-AzEMA) micelle and provided Figures showing the doxorubicin-prodrug is within the micelle, thereby meeting the claimed “encapsulated within said polymeric micelle.”
Ruiz-Hernández further teaches the doxorubicin-prodrug loaded in the mPEG-b-p(HPMAmLac2-co-AzEMA) micelles can be:
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or
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(pages 1677-1678; Fig(s) 2-4).
While doxorubicin prodrug of Ruiz-Hernández contains a single benzyl moiety spacer (n=1) (as circled above – see page 5 of this office action) as opposed to the claimed elected compound, which requires n is 2-6 or in other words, 2-6 benzyl moiety spacers, it would have been obvious to modify the doxorubicin prodrug of Ruiz-Hernández such that the single benzyl moiety spacer is double benzyl spacer moieties in view of the guidance from Aben.
Aben teaches esters of glucuronide prodrug of doxorubicin having the following structure:
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, wherein R1 is H or OCH3; R2 is H or OH; R is a residue having formula:
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, where n is 1 to 40; and p is an integer from 1 to 5, preferably 1 or 2 (Abstract’; [0002]-[0044], [0057]-[0065], [0075]-[0089]; Examples 1, 5-6, 9-10, and 12; claims 1-2, 4, 6, 13 and 14).
It would have been obvious to one of ordinary skill in the art to modify the doxorubicin prodrug such that the single benzyl moiety spacer is double benzyl moiety spacers, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because Aben provided the guidance to do so by teaching that the doxorubicin prodrug of Ruiz-Hernández can be synthesized to have double benzyl moiety spacers, as it is established by Aben that it is well-known in the art the benzyl spacer moiety of the doxorubicin prodrug of Ruiz-Hernández can be a single or a double spacer moiety (Aben: [0002]-[0022], [0070]-[0084]). Thus, it would have been a simple modification from a single benzyl spacer moiety to a double benzyl spacer moiety so as to provide a doxorubicin prodrug that has a desired solubility and hydrolysis, per guidance from Aben, and achieved Applicant’s claimed invention with reasonable expectation of success.
Regarding claims 8, 9 and 21, as discussed above, Ruiz-Hernández teaches the drug loaded in the micelle is doxorubicin, thereby meeting the claimed hydrophilic drug molecule.
Regarding claim 11, Ruiz-Hernández teaches an intravenous composition containing a diluent (PBS) and the doxorubicin-prodrug loaded in mPEG-b-p(HPMAmLac2-co-AzEMA) micelles (page 1675).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of Applicant’s invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Claim(s) 7 and 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ruiz-Hernández et al (Polymer Chemistry, 2014, 5: 1674-1681; cited in IDS filed 01/04/2023) in view of Aben et al (US 2009/0227647 A1), as applied to claim 1 above, and further in view of Lin et al (Abstracts/Journal of Controlled release, 2015, 213: e48-e49).
The polymeric micelle of claim 1 is discussed above, said discussion being incorporated herein in its entirety.
However, Ruiz-Hernández and Aben do not expressly teach platinum compound of claims 7 and 20.
Regarding the platinum compound of claims 7 and 20, Lin teaches mPEG-b-PLG micelles loaded with doxorubicin and cisplatin, and said micelles loaded with the dual drugs (cisplatin and doxorubicin) enabled enhanced (synergistic) therapeutic efficacy, as well as, the cisplatin also stabilized doxorubicin loaded in the micelles (page e48, bottom to right column through page e49, left column; and Fig. 1). Lin teaches the cisplatin (CDDP) is conjugated to the carbonyl groups through coordination bond (page e49, left column).
It would have been obvious to one of ordinary skill in the art to modify the doxorubicin-prodrug of Ruiz-Hernández in view of Aben such that cisplatin is additionally linked to the carbonyl group as depicted as follows:
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, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because Lin provided the guidance to do so by teaching that cisplatin can be loaded with doxorubicin in polymeric micelles by conjugating cisplatin to the carbonyl groups via coordination interaction, and such interaction between the cisplatin and carbonyl groups not only improved stability of the micelles but also enabled synergistic therapeutic efficacy such as enhanced anticancer effect (Lin: page e49, left column). Thus, an ordinary artisan seeking to improved stability of the micelles, as well as, provide a combination therapy that enabled a synergistic anticancer effect, would have looked to modify the doxorubicin-prodrug of Ruiz-Hernández in view of Aben such that cisplatin is additionally linked to the carbonyl group (as shown above), and achieve Applicant’s claimed invention with reasonable expectation of success.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of Applicant’s invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Below is the Examiner’s response to Applicant’s arguments as they pertain to the pending 103 rejections.
Applicant's arguments filed 05/22/2026 have been fully considered but they are not persuasive.
Applicant argues that “Compounds of Formula (I) or (III), having a specific spacer L as recited in claim 1, have several advantages in comparison with compound having a spacer such as in the structure of Ruiz-Hernandez et al. These advantages include improved physicochemical properties, enabling quick formation of well-defined, small and stable polymeric micelles with a relatively high drug loading efficiency. This is described on page 7 of the application as filed.” Applicant alleges that the specification provided comparative experimental data showing said advantages, particularly Experiment 1 and Figure 1, as well as, Experiment 2 and Figure 4. Thus, Applicant alleges that “the micelles of the invention show enhanced drug retention and consequently improved targeted delivery. The presence of more than one aromatic ring in the spacer between the drug and the glucuronic acid part of the prodrug is not described or suggested in Ruiz-Hernandez et al” or Lin et al, alone or in combination. (Remarks, pages 16-20).
In response, the Examiner disagrees. As discussed above in the pending 103 rejection, the elected species of the compound from formula (1a) as recited in dependent claim 5 have been taught and rendered obvious by the combined teachings of Ruiz-Hernandez and Aben. See 103 rejection, pages 4-8 of this office action, said pages being incorporated herein in its entirety.
Applicant’s alleged comparative experimental data as shown in the specification are considered, but found insufficient to obviate the standing 103 rejection over the combined teachings of Ruiz-Hernandez and Aben because the presence of more than one aromatic ring in the spacer between the drug and the glucuronic acid part of the prodrug have been taught and render obvious by the teachings from Aben supra, and the presence of multiple benzyl spacer (linker) is reasonably expected to lower the solubility and hydrolysis of the prodrug. Furthermore, with any evidence of unexpected results, claim 1 must be commensurate in scope with the particular polymeric micelle in Experiments 1 and 2 of the specification used for showing the alleged unexpected advantages. See MPEP §716.02(d).
As a result, for at least the reason discussed above, claims 1-2, 4-11, and 19-23 stand rejected as being obvious and unpatentable over the combined teachings of the cited prior arts in the pending 103 rejections as set forth in this office action.
Conclusion
No claim is allowed.
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/DOAN T PHAN/Primary Examiner, Art Unit 1613
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