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 .
Priority
Acknowledgement is made of the Applicant’s claim of domestic priority to provisional US application 63/391,895 filed 25 July 2022.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-23) in the reply filed on 22 January 2026 is acknowledged. Claims 24-27 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Applicant’s election without traverse of the following compound of formula I in the reply filed on 22 January 2026 is acknowledged. Claims 9-14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
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Applicant’s elected species (above) appears to be free of the art. As such, examination has proceeded to additional species covered by the instant claims.
Status of the Claims
Claims 1-27 are pending.
Claims 9-14 and 24-27 are withdrawn.
Claims 1-8 and 15-23 are rejected.
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 1-8, 15-20, and 22 are rejected under 35 U.S.C. 102a1 as being anticipated by Xiong et al. (Journal of Controlled Release 244 (2016) 63–73).
The Applicant claims, in claim 1, a nanoparticle comprising at least one of the following: i) at least one hypoxia sensitive ligand, ii) at least one lipid and at least one hydrophilic therapeutic agent, and iii) an outer region and an inner core. Claim 1 is interpreted as only requiring one of the three components based on the phrase “at least one of.”
Xiong teaches using polymeric metformin (polymet) for anticancer purposes (pg 64, ¶2). A core is formed from the polymet and PGA-CDDP (i.e. cisplatin) wherein the core is further combined with lipids DOTAP and cholesterol to form a nanoparticle (pg 64, sec 2.5; Fig 1). The total concentration of actives in the core (polymet + CDDP) is 15.8 mM and the total concentration of lipids is 40 mM (pg 65, sec 2.5.1-2.5.2). In a ratio of 8:1 liposome to CDDP conjugates, the resulting percentage of actives in the core is about 5 mol% (15.8 mM actives/ 338.8 mM total concentration) (pg 65, sec 2.5.3). Because only one of the three components of the instant claims must be present, the dependent claims narrowing components i) and iii) are considered optional limitations and thus further covered under this rejection. As such, the resulting lipid nanoparticle comprising both cisplatin and metformin (both hydrophilic actives) in the core of the nanoparticle in about 5 mol%, anticipates instant claims 1-8, 15-20, and 22.
Claims 1-3, 5, 15, 17-18, and 22 are rejected under 35 U.S.C. 102a1 as being anticipated by Chen et al. (Biomedicine & Pharmacotherapy 125 (2020) 109988).
The Applicant claims, in claim 1, a nanoparticle comprising at least one of the following: i) at least one hypoxia sensitive ligand, ii) at least one lipid and at least one hydrophilic therapeutic agent, and iii) an outer region and an inner core. Claim 1 is interpreted as only requiring one of the three components based on the phrase “at least one of.”
Chen teaches a lipid nanoparticle comprising nitroimidazoles (shown below) conjugated to PLA-PEG linkers that are used to form the shell of the nanoparticle (Fig 1, Fig 2). The core of the nanoparticle comprises DDP (cisplatin) (Fig 2).
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The above nitroimidazole anticipates the structure of instant claim 1 wherein M is absent, R1 is C6 alkyl substituted by N(R)2, and wherein R is H.
Because only one of the three components of the instant claims must be present, the dependent claims narrowing components ii) and iii) are considered optional limitations and thus further covered under this rejection. As such, the resulting lipid nanoparticle comprising cisplatin in the core and in the shell of the nanoparticle, anticipates instant claims 1-3, 5, 15, 17-18, and 22.
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 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.
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.
Claims 1-5, 7, and 15-22 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (Biomedicine & Pharmacotherapy 125 (2020) 109988) in view of Laird et al. (Clin Cancer Res; 24(20) October 15, 2018) in view of Sigalov (US 2013/0045161).
The Applicant claims, in claim 1, a nanoparticle comprising at least one of the following: i) at least one hypoxia sensitive ligand, ii) at least one lipid and at least one hydrophilic therapeutic agent, and iii) an outer region and an inner core. Claim 1 is interpreted as only requiring one of the three components based on the phrase “at least one of.”
Chen teaches a lipid nanoparticle comprising nitroimidazoles (shown below) conjugated to PLA-PEG linkers that are used to form the shell of the nanoparticle (Fig 1, Fig 2). The core of the nanoparticle comprises DDP (cisplatin) (Fig 2).
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The above nitroimidazole anticipates the structure of instant claim 1 wherein M is absent, R1 is C6 alkyl substituted by N(R)2, and wherein R is H. Chen teaches that hypoxia targeted drug delivery systems are a promising strategy in cancer therapies (pg 1, ¶2). The above nitroimidiazoles can be incorporated into lipid-polymer hybrid nanoparticles with a polymer core surrounded by a phospholipid layer, which combines the advantages of biodegradable polymeric nanoparticles and biomimetic advantages of liposomes (pg 2, ¶2). The lipid can be DSPE, which is exemplified with a PEG-linked hyaluronic acid (pg 2, sec 2.1-2.2). The nanoparticles of Chen can be used to target various cancers including lung cancer (pg 2, ¶3-4). Regarding the amounts of each agent, Chen teaches using 200 mg of the nitroimidazole polymer to 50 mg of the cisplatin (pg 2, sec 2.3).
Chen does not teach combining nitroimidazole with DSPE in the nanoparticle. Chen does not teach additional therapeutic agents or contrast agents being used in the nanoparticle.
Laird teaches that lung cancer is often treated with chemotherapy of cisplatin and etoposide, however is often met with tumor recurrence (pg 5143, ¶1). Laird teaches the need to complement and enhance current treatments (id) and has found that PARP inhibitors such as talazoparib effectively sensitizes lung cancer cells to irradiation and thus provide a powerful tool to improving lung cancer therapy (abstract).
Sigalov teaches that greater target selectivity and better delivery efficiency are two major goals in the development of imaging contrast agents [0003]. Tumor-targeted contrast agents based on a nanoparticle formulation may offer enhanced sensitivity and specificity for in vivo tumor imaging [0003].
It would have been prima facie obvious to prepare the nanoparticles of Chen wherein the particle is a lipid-polymer hybrid nanoparticle with a polymer core surrounded by a phospholipid layer. Chen teaches the phospholipid layer may comprise DSCE and can be linked by PEG to the nitroimidazole derivative, above. The inner core can comprise the active agent, cisplatin, and the nanoparticle can be used to treat lung cancer. It would have been obvious to further include an additional therapeutic agent, such as talazoparib, in the core based on its known use for treating lung cancer and enhancing the sensitivity of the cancer cells to irradiation. Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use (see MPEP § 2144.07). Moreover, it would have been obvious to further include a contrast agent in the nanoparticle based on the teaching of Sigalov that contrast agents can be used to enhance sensitivity and selectivity of the nanoparticles for in vivo tumor imaging, which would thus enhance the treatment as well.
Regarding the concentration of either the lipid or the therapeutic agent, Chen teaches using 200 mg of the lipid-linked nitroimidazole to 50 mg of the active. While these are not provided in mol%, it can be estimated that the amount of active is greater than 0.025 mol% and less than 95 mol%, and thus reads on instant claim 16.
Regarding instant claim 18, Chen teaches that phospholipids can be used to form the outer shell layer, thus reading on the presence of a hydrophobic therapeutic agent which can be a lipid.
The combination of Chen, Laird, and Sigalov accordingly render obvious instant claims 1-5, 7, and 15-22.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREW S ROSENTHAL whose telephone number is (571)272-6276. The examiner can normally be reached M-F 8-5pm EST.
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/ANDREW S ROSENTHAL/ Primary Examiner, Art Unit 1613