DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on April 21, 2026 has been entered.
Previous Rejections
Applicant’s arguments, filed April 21, 2026, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Status
Claims 12 – 15 have been cancelled.
Claims 1 – 11 and 16 – 24 are examined here-in.
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 non-obviousness.
Claims 1, 2, 4 - 10, 16, 17, and 19 - 24 are rejected under 35 U.S.C. 103 as being unpatentable over Phillips ("Rhenium=186 liposomes as convection-enhanced nanoparticle brachytherapy for treatment of glioblastoma" Neuro-Oncology 2012, of record) in view of Chamberlain (“Leptomeningeal metastasis: a response assessment in neuro-oncology critical review of endpoints and response criteria of published randomized clinical trials” Neuro-Oncology 2014, of record).
Phillips teaches a method for administering radiolabeled liposomes to a subject for the treatment of glioblastoma (page 420 column 1). Phillip’s liposomes were radiolabeled with rhenium-186 BMEDA (N,N-bis(2-mercaptoethyl)-N’,N’-diethylenediamine) (page 418 column 1).
Phillips teaches that 2 mL liposomes with 60 mM total lipid were labeled with rhenium-186 BMEDA containing 115 mCi (page 418 column 1), then 25 µL were injected (page 420 column 2).
Phillips teaches that rhenium-186 BMEDA was loaded into liposomes via an ammonium pH gradient (page 418).
Phillips’ liposomes were composed of distearoylphosphatidylcholine and cholesterol (page 417 column 2).
Phillips teaches that the liposomes were administered by convection-enhanced delivery (page 418 column 2) with infusion of volumes of 50 µL and 100 µL into subjects at a rate of 2 µL/min (page 420 column 1).
Phillips teaches that during convection-enhanced delivery of radiolabeled liposomes the subjects were imaged by SPECT/CT (page 418 column 2, figures 1 and 2). Then, further SPECT imaging was done subsequent to radiolabeled liposome administration (page 418 column 2).
Phillips does not teach the treatment of leptomeningeal metastases (claim 15).
Chamberlain teaches the missing element of Phillips.
Chamberlain shows several studies that have examined liposomal delivery of chemotherapeutic drugs as compared to the administration of free drug for the treatment of leptomeningeal metastases (Table 1). Chamberlain teaches that liposomal therapies had superior efficacy in the treatment of leptomeningeal metastases compared to non-liposomal treatments (abstract).
The combination of Phillips’ and Chamberlain’s teachings renders claims 1, 2, 4 - 10, 16, 17, and 19 - 24 prima facie obvious as combining prior art elements according to known methods to yield predictable results (MPEP 2143(i)(a)). A person of ordinary skill in the art would have been motivated to apply the method of Phillips for administering radiolabeled liposomes to subjects (page 420 column 1) with leptomeningeal metastases because Chamberlain teaches that liposomal therapies have superior efficacy in the treatment of leptomeningeal metastases compared to non-liposomal therapies (abstract). Therefore, the combination of known prior art elements (a method for administering radiolabeled liposomes, liposomal treatments for leptomeningeal metastases) would yield predictable results (i.e. a method for administering radiolabeled liposomes for treatment of leptomeningeal metastases) which is prima facie obvious according to MPEP 2143(i)(a).
Phillips’ method for administering 186Re-labeled liposomes to a subject for the treatment a cancer (page 420 column 1) in combination with Chamberlain’s teaching that liposomal therapies have superior efficacy in the treatment of leptomeningeal metastases (abstract) reads on claim 1. A person of ordinary skill in the art would have been motivated to apply the method of Phillips for administering radiolabeled liposomes to subjects (page 420 column 1) to treat leptomeningeal metastases as taught by Chamberlain because Chamberlain teaches that liposomal therapies have superior efficacy in the treatment of leptomeningeal metastases compared to non-liposomal therapies (abstract).
Phillips teaches that 2 mL liposomes with 60 mM total lipid were labeled with rhenium-186 BMEDA containing 115 mCi (page 418 column 1), then 25 µL were injected (page 420 column 2). With consideration of the injection volume (25 µL) being 1/80th of the initial liposome formulation volume (2 mL), approximately 1.4 mCi is present in the 25 µL fraction. Phillips’ teaching of 1.4 mCi overlaps on the instantly claimed range of 1 to 250 mCi as recited in instant claim 1. Claimed ranges that overlap with teachings of the prior art are prima facie obvious according to MPEP 2144.05(i). Notably, the instant specification states that the term “delivered” is interchangeable with the term “administered” (paragraph 0059), therefore the administration of 1.4 mCi in 25 µL reads on the limitation of “delivered to” in claim 1.
Phillips’ use of rhenium-186 BMEDA reads on claims 2 and 4 of the instant application, which recite R groups for the radiolabeled compound that are consistent with BMEDA (claim 2) and that the metal is rhenium-186 (claim 4).
Phillips’ teaching that rhenium-186 BMEDA was loaded into liposomes via an ammonium pH gradient (page 418 column 1) reads on claim 5 of the instant application which recites the compound is incorporated into the liposome.
Phillips’ teaching for liposomes composed of distearoylphosphatidylcholine and cholesterol (page 417 column 2) reads on claims 6 – 9 of the instant application which recite that the liposomes are comprised of a lipid (claim 6), a phospholipid (claim 7), a cholesterol or cholesterol analogue (claim 8), and distearoyl phosphatidylcholine (claim 9).
Phillips teaches that 2 mL liposomes with 60 mM total lipid were labeled with rhenium-186 BMEDA containing 115 mCi (page 418 column 2). By the Examiner’s calculations, 2 mL of liposomes with 60 mM total lipid (DSPC: cholesterol 55:45 molar ratio) is approximately 81 mg of lipid. 115 mCi per 81 mg of lipid is approximately equal to 71 mCi per 50 mg of lipid, which is within the range of 0.01 mCi to 400 mCi per 50 mg of lipid as recited in claim 10 of the instant application. Claimed ranges that overlap with those taught by the prior art are prima facie obvious according to MPEP 2144.05(i).
Phillips’ teaching that the liposomes were administered by convection-enhanced delivery (page 418 column 2) with infusion of volumes of 50 µL and 100 µL into subjects at a rate of 2 µL/min (page 420 column 1) reads on claims 16, 17, 19, and 21. Administration via infusion reads on claim 16. Administration via convection-enhanced delivery reads on claim 17. Infusion at a rate of 2 µL/min reads on claim 19. Infusion of 100 µL, which is equal to 0.1 mL, overlaps on the claimed range of 0.1 mL to 25 mL, as recited in claim 21 of the instant application.
Phillips’ teaching of 1.4 mCi radioactivity injected in a liposome solution (page 418 column 1, page 420 column 2) overlaps on the instantly claimed range of 1 to 50 mCi as recited in instant claim 20. Claimed ranges that overlap with teachings of the prior art are prima facie obvious according to MPEP 2144.05(i).
With similar calculations as above, Phillips’ teaching for 2 mL liposome solution containing 115 mCi (page 418 column 1) is approximately 57.5 mCi/mL. Although 57.5 mCi/mL does not overlap the instantly claimed range of about 0.1 to about 50 mCi/mL as recited in claim 22, it is very close, and absent a showing of criticality the difference between the claimed range and Phillips’ teaching is negligible, therefore 57.5 mCi/mL is prima facie obvious according to MPEP 2144.05(i).
Phillips’ teaching of imaging radiolabeled liposomes during convection-enhanced delivery (page 418 column 2, figures 1 and 2) reads on claim 23 of the instant application.
Phillips’ teaching of imaging radiolabeled liposomes after administration (page 418 column 2) reads on claim 24 of the instant application.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Phillips (as cited above) in view of Chamberlain (as cited above) and further in view of Bao ("A novel liposome radiolabeling method using 99mTC-"SNS/S" complexes: in vitro and in vivo evaluation" Journal of Pharmaceutical Sciences 2003, of record).
The combination of Phillips and Chamberlain does not teach the radiolabeled compound has R groups of R1 is CH2CH2CH2CH3 and R2 is CH2CH2N(CH2CH2SH)(CH2CH2CH2CH3) (claim 3).
Bao teaches the missing element of the combination of Phillips and Chamberlain.
Bao teaches liposomes radiolabeled with 99mTc BMBuA (N,N-bis(2-mercaptoethyl)-1-butylamine) (page 1894), suggesting that different compounds may result in different labeling efficiencies (abstract). Bao’s experiments showed that BMBuA labeling had increased efficiency over the other compounds evaluated (Table 1).
The combination of Phillips, Chamberlain, and Bao’s teachings renders claim 3 prima facie obvious as combining prior art elements according to known methods to yield predictable results (MPEP 2143(i)(a)). A person of ordinary skill in the art would have been motivated to modify the method of Phillips and Chamberlain to include BMBuA as taught by Bao because Bao teaches that BMBuA has increased labeling efficiency over other compounds. This combination would be expected to yield radiolabeled liposomes with increased labeling efficiency, therefore, the combination of known prior art elements would yield predictable results which is prima facie obvious according to MPEP 2143(i)(a).
The combination of Phillips and Chamberlain’s teachings for a method of administering radiolabeled liposomes to a subject (Phillips page 420 column 1) to treat leptomeningeal metastases (Chamberlain abstract) with Bao’s teachings of radiolabeling liposomes with 99mTc BMBuA (abstract, Table 1) reads on R1 is CH2CH2CH2CH3 and R2 is CH2CH2N(CH2CH2SH)(CH2CH2CH2CH3) as recited in claim 3 of the instant application.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Phillips (as cited above) in view of Chamberlain (as cited above) and further in view of Li (Li, S. et al. “Feasibility of eradication of breast cancer cells remaining in post-lumpectomy cavity and draining lymph nodes following intracavitary injection of radioactive immunoliposomes” Molecular Pharmaceutics 2012, of record).
The combination of Phillips and Chamberlain does not teach the treatment molecules attached to the liposomes (claim 11).
Li teaches the missing element of the combination of Phillips and Chamberlain.
Li teaches a method for administering radiolabeled liposomes to a subject for the treatment of breast cancer (page 2515 column 2). Li teaches that panitumumab and bevacizumab, two monoclonal antibodies, are conjugated to the radiolabeled liposomes (page 2514 column 2).
The combination of Phillips, Chamberlain, and Li’s teachings renders claim 11 prima facie obvious as combining prior art elements according to known methods to yield predictable results (MPEP 2143(i)(a)). A person of ordinary skill in the art would have been motivated to modify the method of Phillips and Chamberlain to include attached treatment molecules as taught by Li (page 2514 column 2) in order to add therapeutic benefit to the liposomes. This combination would be expected to yield radiolabeled liposomes with added therapeutic benefits, therefore, the combination of known prior art elements would yield predictable results which is prima facie obvious according to MPEP 2143(i)(a).
The combination of Phillips and Chamberlain’s teachings for a method of administering radiolabeled liposomes to a subject (Phillips page 420 column 1) to treat leptomeningeal metastases (Chamberlain abstract) with Li’s teaching of monoclonal antibodies attached to the liposome (page 2514 column 2) reads on claim 11 of the instant application because monoclonal antibodies are treatment molecules.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Phillips (as cited above) in view of Chamberlain (as cited above) and further in view of Mehta (“Convection-Enhanced Delivery” Neurotherapeutics 2017, of record).
The combination of Phillips and Chamberlain does not teach that the convection-enhanced delivery comprises the administration of the radiolabeled liposomes via one or more catheters (claim 18).
Mehta teaches the missing element of the combination of Phillips and Chamberlain.
Mehta teaches that convection-enhanced delivery is a technique for delivering therapeutics to other neuro-centric diseases (abstract). Mehta teaches that convection-enhanced delivery allows for the bypassing of the blood-brain barrier (which traditionally hampers drug delivery for neurological diseases), allows for targeted delivery, and the perfusion of target sites (page 358 column 2 to page 359 column 1). Mehta teaches that one or more catheters are used to deliver compounds for convection-enhanced delivery (page 359 column 1).
The combination of Phillips, Chamberlain, and Mehta’s teachings renders claim 18 prima facie obvious as combining prior art elements according to known methods to yield predictable results (MPEP 2143(i)(a)). A person of ordinary skill in the art would have been motivated to modify the method of Phillips and Chamberlain to include one or more catheters as taught by Mehta (page 359 column 1) because Mehta teaches that convection-enhanced delivery (i.e. the method of delivery taught by Phillips) requires one or more catheters. Each of the prior art elements taught by Phillips, Chamberlain, and Mehta were known before the effective filing date of the instant application, and their combination would be expected to yield predictable results which is prima facie obvious according to MPEP 2143(i)(a).
The combination of Phillips and Chamberlain’s teachings for a method of administering radiolabeled liposomes to a subject (Phillips page 420 column 1) to treat leptomeningeal metastases (Chamberlain abstract) with Mehta’s teaching that one or more catheters are used in convection-enhanced delivery (page 359 column 1) reads on claim 18 of the instant application.
Examiner’s Reply to Attorney Arguments Dated April 21, 2026
Applicant argues that the prior art of combination of Phillips and Chamberlain does not provide a person of ordinary skill in the art a reasonable expectation of success for arriving at the amount of radioactivity delivered to the central nervous system by the radiolabeled liposomes as recited in instant claim 1 (Remarks page 6). The Examiner disagrees, because as noted in the body of the rejection above, Phillips teaches that 2 mL liposomes with 60 mM total lipid were labeled with rhenium-186 BMEDA containing 115 mCi (page 418 column 1), then 25 µL were injected (page 420 column 2). With consideration of the injection volume (25 µL) being 1/80th of the initial liposome formulation volume (2 mL), approximately 1.4 mCi is present in the 25 µL fraction. Phillips’ teaching of 1.4 mCi overlaps on the instantly claimed range of 1 to 250 mCi as recited in instant claim 1. Notably, the instant specification states that the term “delivered” is interchangeable with the term “administered” (paragraph 0059), therefore the administration of 1.4 mCi in 25 µL reads on the limitation of “delivered to” in claim 1.
Since the terms “delivered” and “administered” are interchangeable according to the instant specification (paragraph 0059), Phillips’ teaching for the administration of 1.4 mCi in 25 µL overlaps on the instantly claimed range of 1 to 250 mCi as recited in amended claim 1. Claimed ranges that overlap with teachings of the prior art are prima facie obvious according to MPEP 2144.05(i).
Conclusion
All claims are rejected. No claims are allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Toriana N. Vigil whose telephone number is (571)270-7549. The examiner can normally be reached Monday - Friday 9:00 a.m. - 5:00 p.m. EST.
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/TORIANA N. VIGIL/Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
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